APRI Score Research Articles

Safety and efficacy of sofosbuvir/ledipasvir combination in treatment of chronic hepatitis C infection in adolescents aged 12–17 years old

BackgroundChronic hepatitis C virus (CHC) infection represents a crucial health problem, especially among children and adolescents. The ledipasvir (LDV)/sofosbuvir (SOF) regimen has been approved to treat adolescents (aged 12 to 17 years old) infected with hepatitis C virus (HCV) genotypes 1, 4, 5, and 6 and then extended to include children above or equal to 3 years old. The current study aims to evaluate the safety and efficacy of SOF/LDV combination in treating CHC-infected 12- to 17-year-old adolescents.Patients and methodsThis retrospective cohort study was performed on 147 Egyptian adolescents with CHC. The patients were treated with SOF 400 mg/LDV 90 mg combination once daily for 12 weeks. Possible side effects and laboratory data including HCV ribonucleic acid polymerase chain reaction (RNA PCR), complete blood count (CBC), and liver tests were recorded at baseline and week 12 after the end of treatment (EOT).ResultsSustained virological response 12 weeks (SVR12) after end of treatment (EOT) was observed in 146 out of 147 patients (99.3%). The treatment regimen was efficiently tolerated with no reported cases of discontinuation caused by intolerability. Moreover, the side effects were minimal; 71.4% of the patients did not report any side effects related to the treatment. However, the rest mentioned fatigue, headache, or both of them. Fatigue was the main side effect reported in 16.3% of the patients. Furthermore, ALT and AST levels were normalized after treatment. FIB-4 and APRI scores were statistically significantly decreased 2 years post-SVR, in comparison to their levels before treatment, from 0.34 and 0.36 to 0.25 and 0.17, respectively.ConclusionThe LDV/SOF regimen is one of the safe regimens used to treat adolescent patients with CHC infection.

Hospital Mortality in Acute Decompensation of Alcoholic Liver Cirrhosis: Can Novel Survival Markers Outperform Traditional Ones?

Background: There is a strong correlation between systemic inflammation intensity and clinical presentation, disease progression, and survival during liver cirrhosis decompensation. This study aimed to evaluate the prognostic performance of blood-based biomarkers as meta-inflammation markers, including NLR, PLR, LMR, INPR, MPR, ALBI, FIB4, and APRI, in predicting hospital mortality in patients with acute decompensation of alcohol-related liver cirrhosis. Methods: Data from 411 patients with their first onset of acute decompensation were analyzed, forming two groups: deceased and survived during hospitalization. Generalized partial least squares regression analysis was applied to explore the effects of surrogate indicators on mortality rates, using mortality rate as the dependent variable. Root Mean Square Error, Akaike's, and Bayesian information criteria determined that four components accounted for most of the variance. Results: Variables with significant negative contributions to the outcome prediction (ranked by standardized regression coefficients) were encephalopathy grade, total bilirubin, Child-Turcotte-Pugh score, MELD, NLR, MPV, FIB4, INR, PLR, and ALT. Coefficient sizes ranged from -0.63 to -0.09, with p-values from 0 to 0.018. Conclusions: NLR, PLR, and FIB4 significantly contribute to hospital mortality prediction in patients with acute decompensation of alcohol-related liver cirrhosis. Conversely, some variables used to predict liver disease severity, including INPR, APRI, LMR, and ALBI score, did not significantly contribute to hospital mortality prediction in this patient population.

Serum collagen IV as a predictor for response to direct-acting antivirals hepatitis C therapy

ABSTRACT Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4–25.2) vs.9.7 (7.2–12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.

A-040 Association of GATA-4 and Platelet Derived Growth Factor-B in Metabolic (Dysfunction) Associated Fatty Liver Disease

Abstract Background Metabolic (dysfunction) associated fatty liver disease is a global concern as its prevalence is rising steeply ranging from 38.7% to 50.7%. MAFLD is a multifaceted burden of diseases such as diabetes, obesity, and cardio-metabolic diseases. It is the leading cause of hepatocellular carcinoma. GATA-4 is a zinc finger transcription factor located in liver sinusoidal endothelial cells and plays a critical role in liver regeneration. Platelet-derived growth factor-B (PDGF-B) plays a role in the profibrogenic trans-differentiation of Hepatic stellate cells and is actively involved in the development of hepatic fibrosis. Therefore, the study hypothesized that GATA-4 and PDGF-B are dysregulated and involved in the progression of MAFLD. Thus, the study aimed to assess the association of GATA 4 and PDGF-B in MAFLD, disease control, and healthy control. Methods 80 subjects were recruited after exclusion criteria from Gastroenterology and Medicine OPD at AIIMS, New Delhi, and divided into 3 groups: Group 1 (healthy control)-20, Group 2 (disease control)-20, and Group 3 (MAFLD)-40. Institutional ethical committee approval was obtained. The demographic and anthropometric details, blood investigations, Non-invasive scores (AST/ALT ratio, APRI &amp; FIB-4), and Transient elastography findings were illustrated in all the groups. The correlation between the GATA-4, PDGF-B, and platelet indices (MPV, P-LCR, PDW, and PCT) was done. STATA version 15 software was used for statistical analysis. Results GATA 4 was significantly decreased (p&amp;lt;0.001) and PDGF-B (p&amp;lt;0.001) was significantly increased in MAFLD subjects compared to healthy controls. However, no significant correlation was observed between GATA-4 and PDGF-B with platelet indices (P-LCR, PCT, and PDW). In contrast, mean platelet volume (MPV) was statistically significant (p&amp;lt;0.001) but it was clinically insignificant between the study groups. Similarly, HOMA-IR and GATA-4 did not show any significant correlation among MAFLD. However, CAP, LSM parameters of Transient elastography, APRI, and FIB-4 scores were statistically significant (p&amp;lt;0.001) in MAFLD when compared to healthy control. AUROC of non-invasive scores were found with weak discrimination and clinically not robust to distinguish the fibrosis grading. Conclusions GATA-4 and PDGF-B could be potential biomarkers, as no drugs are available so far to fill the global gap. However, pharmacological aspects need to be formulated for the treatment of MAFLD.

Serum ECM1 is a promising biomarker for staging and monitoring fibrosis in patients with chronic hepatitis B.

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl4-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.

Analysis of Calculated Liver Scores for Long-Term Outcome in 423 Cutaneous Melanoma Patients.

Background: Neoadjuvant and adjuvant therapies are currently getting increasingly important in cutaneous melanoma (CM) management. However, there is still a lack of prognostic tools to identify which patients have a poor prognosis. There is increasing evidence that the liver score may be a potential prognostic parameter in different tumour types. The aim was to investigate whether established liver scores can establish the prognosis of CM. Methods: According to established methods, the APRI, the MELD score, the MELD-Na score and the De Ritis ratio were calculated from the laboratory values at the time of the initial diagnosis. Survival was compared with the Kaplan-Meier curve and tested with log-rank tests. Risk factors associated with cutaneous melanoma-specific survival (CMSS) and progression-free survival (PFS) were assessed by using the Cox proportional hazards regression model. To determine the diagnostic accuracy, we performed a time-dependent ROC analysis. Results: A total of 423 patients were included, including 141 patients in AJCC stage (2017) I (33.3%), 82 in stage II (19.4%), 128 in stage III (30.3%) and 72 in stage IV (17%). Median time until melanoma-specific death was 99 months (IQR: 37-126). In addition, 37.6% of patients relapsed with a median time to relapse of 88 months (IQR: 17.5-126). In all stages, tumour thickness and ulceration were independent markers for predicting CMSS and PFS (p < 0.05). The multivariable analysis with all stages showed no significant association with CM outcome for liver scores (p > 0.05). The subgroup analysis revealed that the APRI (≥0.2241) was associated with CMSS and PFS in melanoma stages I and II, independently of tumour thickness, age and ulceration (HR 2.57, 95% CI 1.14-5.75; HR 2.94, 95% CI 1.42-6.09, respectively). Conclusions: The 20-year prognosis of AJCC stage I and II CM was dependent on tumour thickness and the APRI. High tumour thickness and an APRI ≥ 0.2241 at the initial diagnosis were associated with a worse prognosis. Future studies should investigate the independent prognostic value of the APRI in low-stage CM. Furthermore, the APRI score could be a potential biomarker for nomograms.

Comparison of blood-based liver fibrosis scores in the Mount Sinai Health System, MASLD Registry, and NHANES 2017-2020 study.

Liver fibrosis is a critical public health concern, necessitating early detection to prevent progression. This study evaluates the recently developed LiverRisk score and steatosis-associated Fibrosis Estimator (SAFE) score against established indices for prognostication and/or fibrosis prediction in 4diverse cohorts, including participants with metabolic dysfunction-associated steatotic liver disease (MASLD). We used data from the Mount Sinai Data Warehouse (32,828 participants without liver disease diagnoses), the Mount Sinai MASLD/MASH Longitudinal Registry (422 participants with MASLD), and National Health and Nutrition Examination Survey 2017-2020 (4133 participants representing the general population) to compare LiverRisk score, FIB-4 index, APRI, and SAFE score. Analyses included Cox proportional hazards regressions, Kaplan-Meier estimates, and classification metrics to evaluate performance in prognostication and fibrosis prediction. In Mount Sinai Data Warehouse, LiverRisk score was significantly associated with future liver-related outcomes but did not significantly outperform FIB-4 or APRI for predicting any of the outcomes. In the general population, LiverRisk score and SAFE score outperformed FIB-4 and APRI in identifying fibrosis, but LiverRisk score underperformed among participants who were non-White or had type 2 diabetes. Among participants with MASLD, SAFE score outperformed FIB-4 and APRI in 1 of 2 cohorts, but there were generally few significant performance differences between all 4 scores. LiverRisk score does not consistently outperform existing predictors in diverse populations, and further validation is needed before adoption in settings with significant differences from the original derivation cohorts. It remains necessary to replicate the ability of these scores to predict liver-specific mortality, as well as to develop diagnostic tools for liver fibrosis that are accessible and substantially better than current scores, especially among patients with MASLD and other chronic liver conditions.

Association between Helicobacter pylori infection, MASLD, and liver fibrosis in patients with severe obesity: a single-center experience.

Our study sought to evaluate if an association exists between Helicobacter pylori (H. pylori), metabolic dysfunction- associated steatotic liver disease (MASLD), and liver fibrosis in patients with severe obesity (BMI > 35). Our retrospective study included 584 patients over the age of 18years with severe obesity, who underwent preoperative liver transient elastography (VCTE), upper endoscopy, blood work, and intra-operative liver biopsy concurrent with bariatric surgery at a single institution from July 2020 to September 2021. Liver fibrosis scores including FIB-4, APRI, NAFLD fibrosis score, BARD score, AST: ALT ratio, and NAFLD activity score (NAS) were calculated from the laboratory results and liver biopsy findings. The presence or absence of H. pylori was determined based on gastric biopsies obtained during upper endoscopy. Other variables collected included age, gender, mean preoperative weight, BMI, and the presence or absence of comorbidities. Student's t-test and non-parametric testing were used for the analysis of continuous variables and Chi-square analysis was used for categorical data. Of the 584 patients, 14.7% were H. pylori positive and 85.3% were negative. Liver fibrosis scores including FIB-4, APRI, and NAFLD fibrosis scores were significantly higher in the positive group (p < 0.05), but there was no difference in AST: ALT ratio and BARD score. A significantly higher VCTE steatosis and fibrosis scores were noted in the H. pylori-positive group (p < 0.05). Similarly, a significantly higher NAS (NAFLD activity score) on liver biopsies was noted in the positive group, with all the individual components of NAS (steatosis, lobular inflammation, and hepatocyte ballooning) being significantly higher in the positive group (p < 0.05). A significantly higher incidence of fibrosis on liver biopsies was noted in the positive group overall and across all stages of fibrosis (p < 0.05). There were no significant differences between the groups in relation to gender, mean weight, BMI, presence of comorbidities including Diabetes Mellitus, and laboratory values. Our study demonstrates that H. pylori colonization or infection is associated with a higher risk of development of MASLD and progression to fibrosis. Further, population-based studies are needed to corroborate our findings.

Correlations Between Viro-Immunologic Status of the Newly Diagnosed Patient with HIV Infection and Liver Damage

Abstract Liver damage can be a direct consequence of human immunodeficiency virus infection or indirect mechanisms triggered by human immunodeficiency virus. Hepatic fibrosis may be present in patients newly diagnosed with HIV infection or in those with viro-immunologic failure after initiation of antiretroviral therapy. In the present study we evaluated biologically and viro-immunologically the 351 patients newly diagnosed with HIV infection in the Regional Center Constanta between 01.01.2015 and 31.06.2024, subsequently re- evaluated one year after diagnosis and institution of specific medication. Liver fibrosis stage was assessed using APRI, FIB4 and FORNS scores. The cohort comprised 351 patients, 313 with HIV monoinfection. The mean age at diagnosis was 36.09 years, predominantly male (237 patients). The median CD4+ cell count was 269.5 cells/mm3, and the median HIV-RNA was 164 x103 copies/mL. Most cases were CDC staged A2 (91 cases) and C3 (77 cases). Patients with HIV monoinfection showed a significant association between CD4+ cell level and ALT (p=0.026) and AST (p&lt;0.001), respectively. We observed statistically significant correlation between AST and viral load values (p=0.003 in monoinfection and 0.042 in coinfection). APRI, FIB4 and FORNS scores averaged higher in the coinfected group compared to the HIV monoinfected group. Statistically significant associations were found between APRI, FIB4, FORNS scores and CD4+ cell counts and HIV viral load values, respectively.

High Diagnostic Value of Transient Elastography for Advanced Fibrosis and Cirrhosis in Patients With Chronic Hepatitis Delta

Liver biopsy remains the gold standard for fibrosis staging in patients with chronic hepatitis delta (CHD). Here we comparatively evaluated the performance of transient elastography (TE) and biomarkers for the diagnosis of liver fibrosis in patients with CHD. 230 HDV-infected RNA-positive patients from various centers who underwent liver biopsy and liver stiffness measurements (LSM) using Fibroscan®, within a period of 6 months maximum, were investigated retrospectively. AUROC and Youden index were used to establish cut-off values of LSM. TE was compared with other noninvasive tests (NITs): APRI, Fibrosis-4 and Delta-4 fibrosis scores. Histologic fibrosis stage distribution was: 20.4% for F0-F1; 27.0% for F2; 18.7% for F3 and 33.9% for F4. TE demonstrated good diagnostic performance for detecting cirrhosis and advanced fibrosis with AUROC of 0.88 and 0.86, values, which were significantly higher than those obtained with the other NITs (P = .004 and P < .001). With a cutoff value >12 kPa for cirrhosis, sensitivity was 70.5%, specificity 86.2%, positive predictive value (PPV) 72.4% negative predictive value (NPV) 85.1% and accuracy 80.9%. Using 10.4 kPa as cut-off value for F3, sensitivity was 70.2%, specificity 83.5%, PPV 82.5%, NPV 71.7% and accuracy 76.5%. In 89% of patients with LSM ≤ 6.2 kPa, liver biopsy disclosed only absent or minimal fibrosis. TE demonstrated good diagnostic performance for advanced fibrosis and cirrhosis in CHD patients. Advanced fibrosis is highly probable for LSM values ≥10 kPa. LSM values < 6 kPa almost totally exclude significant fibrosis. Between 6 and 10 kPa, liver biopsy should be discussed.

Prognostic Indicators of Morbidity and Mortality in Children with Congestive Hepatopathy Presenting with Ascites.

Objectives: Congestive hepatopathy is a significant complication for children suffering from right-sided heart disease (RHD). We hypothesize that hospitalized pediatric patients with ascites will have congestive hepatopathy leading to advanced liver disease if their cardiac condition is RHD versus non-right-sided heart disease (NRHD). Methods: This is a retrospective cohort study of pediatric patients who presented with an ascites diagnosis (ICD-10 R18) and at least one cardiac diagnosis. Patient demographics, past medical history, laboratory values, imaging results, calculated clinical scores (e.g., APRI, FIB-4), treatment, length of stay (LOS), and death at hospital discharge were analyzed. Results: Of the 136 patients with ascites, 21 patients presented with a primary cardiac disease (12 in RHD and 9 in NRHD). Of these patients, eight (38%) were female, and nine (43%) were White, seven (33%) were Black, and five (24%) were unknown. The RHD group had a mean age of 5.1 Y (vs. 9.5 Y in NRHD). The mean APRI score in RHD patients was 2.87, and it was 0.85 in NRDH. Treatments were similar, with most patients requiring diuretics (11 RHD (92%) vs. 8 NRDH (89%)); 5 RHD (42%) vs. 4 NRDH (44%) required inotropic support. RHD patients had a longer LOS, with an average of 92 days vs. 52 days for NRDH patients. Overall, each group had one death at discharge (8% RHD vs. 11% NRDH). Conclusions: In the realm of children with ascites, the subset grappling with congestive heart disease paints a unique picture. In this context, ascites stands as an elusive predictor of liver decompensation, defying conventional diagnostic pathways.

Assessment of Galectin 3 as a New Biomarker of Liver Fibrosis in Chronic HCV Egyptian Patients and its Correlation to Transient Elastography, FIB-4 Index, and APRI Score

Abstract Background Invasive liver biopsy is the current method for the assessment of liver fibrosis. In search of noninvasive alternatives, galectin-3-binding protein (G3BP) was introduced as a candidate-marker of hepatitis C-related fibrosis based on serum proteomics. Aim of the Work to evaluate serum Galectin-3 as a marker of liver fibrosis and correlate it to the stage of fibrosis assessed by FibroScan, FIB-4 index and APRI score Patients and Methods This was prospective study, was carried out on 30 patients with liver fibrosis/cirrhosis due to chronic HCV inthe Hepatic Virology Unit and the gastroenterology department of Ain Shams university hospitals and 30 health controls with normal, non fibrotic and non cirrhotic, liver, from January 2022 to June 2022 Results There were high significant difference between both groups as regard Serum level of Galectin-3 and APRI score. Conclusion Serum level of galectin-3 was highly expressed in chronic HCV Egyptain patients and positively correlated to FIB-4 index, APRI score and fibroscan.so the serum level of galectin-3 beside other modalities, lab investigations and clinical examination may guide us about the progression to fibrosis and cirrhosis in those patients. In these patients, if galectin-3 levels were found to be high, serum alpha-feto protein level and ultrasonographic examination could be repeated at more frequent intervals. This may also guide us in terms of the treatment plan. Measurement of galectin-3 in sera of large number of patients and follow up may pave the way to pick up early fibrosis and showed its prognostic effect.

Angiopoietin-2 as a Predictor of Fibrosis Regression in Hepatitis C Virus-Patients after Direct Acting Antiviral Drugs

Abstract Background HCV infection is a major health concern. Disease progression to fibrosis, cirrhosis, and HCC is aided by the persistence of inflammatory reactions and cellular damage. Moreover, angiogenesis was found to have a substantial pathogenic role in disease progression. Serum Angiopoietin-2 appears to be correlated with liver stiffness in chronic HCV and its elevation is linked to disease progression from chronic hepatitis to cirrhosis. Aim of the Work The aim of this study was to evaluate the role of serum Angiopoietin-2 in the prediction of regression of fibrosis in chronic HCV patients receiving direct-acting antiviral agents. Patients and Methods Forty Egyptian chronic HCV patients for whom direct-acting antiviral agent (DAA) therapy was planned were included. All patients underwent assessment twice, at baseline and at SVR12, for standard laboratory tests, measurement of fibrosis using FibroScan, FIB-4 and APRI scores, and Angiopoietin-2 level. Results Among 40 patients; 26 (65%) are males and 14 (35%) are females. Their age is ranged between 35 and 60 years old with a mean age of 52.35 ± 6.08 and a median of 53.0 (50.0 – 57.0). The HCV-RNA titer is ranged from 3.60 to 7.20 log IU/mL with a mean titer of 5.99 ± 0.87 before treatment. The median is 6.20 (5.30 – 6.65). There was a significant improvement concerning the fibrosis stage after DAA treatment. Liver fibrosis indices were significantly associated with regression of liver fibrosis stage based on FibroScan data after DAA therapy. Liver size, spleen size and portal vein diameter were improved significantly after successful HCV eradication by DAAs. There was improvement in the Child-Pugh score after successful HCV eradication by DAAs but the difference was no statistically significant (p = 0.500). Baseline Ang-2 was statistically significant after successful HCV eradication by DAAs (p &amp;lt; 0.001). Overall, there was a positive significant correlation between Ang-2 and all the fibrosis stages (p = 0.001) and there was a statistically significant higher mean of Ang-2 in higher stages of liver fibrosis before treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa before treatment. Ang-2 in higher stages of liver fibrosis after treatment. Indeed Ang-2 increase significantly when the fibrosis stage increased and vice-versa after treatment. The correlation between Ang-2 and fibrosis group (F0, F1, F2 &amp; F3) were significant and the correlation between Ang-2 and the liver fibrosis stage (F4) were also significant before treatment. The correlations between Ang-2 levels and fibrosis group (F0, F1, F2 &amp; F3) were significant as well as the advanced liver fibrosis (F4) after DAA therapy. Conclusion Angiopoietin-2 can be a useful predictor of fbrosis regression in chronic HCV patients receiving direct acting antiviral agents. Elevated baseline Angiopoietin-2 and advanced ibrosis stages may predict non-regression of liver fibrosis.

A non-invasive diagnostic nomogram for CHB-related early cirrhosis: a prospective study

This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis patients with chronic hepatitis B (CHB) which cannot be detected by conventional non-invasive examination methods but can only be diagnosed through invasive liver puncture for pathological examination. 72 patients with CHB were enrolled in this prospective study, and divided into S4 stage of liver cirrhosis and S0-S3 stage of non-liver cirrhosis according to pathological findings. Binary logistic regression analysis was performed to identify independent predictors, and a diagnostic nomogram was constructed for CHB-related early cirrhosis. It was validated and calibrated by bootstrap self-extraction. Binary logistic regression analysis showed that age (OR 1.14, 95% CI (1.04–1.27)), right hepatic vein diameter (OR 0.43, 95% CI 0.23–0.82), presence or absence of nodules (OR 31.98, 95% CI 3.84–266.08), and hepatic parenchymal echogenicity grading (OR 12.82, 95% CI 2.12–77.51) were identified as independent predictive indicators. The nomogram based on the 4 factors above showed good performance, with a sensitivity and specificity of 90.70% and 89.66%, respectively. The area under the curve (AUC) of the prediction model was 0.96, and the predictive model showed better predictive performance than APRI score (AUC 0.57), FIB-4 score (AUC 0.64), INPR score (AUC 0.63), and LSM score (AUC 0.67). The calibration curve of the prediction model fit well with the ideal curve, and the decision curve analysis showed that the net benefit of the model was significant. The nomogram in this study can detect liver cirrhosis in most CHB patients without liver biopsy, providing a direct, fast, and accurate practical diagnostic tool for clinical doctors.

Diagnostic Role of Non-Invasive Risk Scores in Prediction of Simple Steatosis versus Non-Alcoholic Steatohepatitis

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is currently considered one of the most common liver diseases in the Western world. NAFLD includes a spectrum of diseases from simple fatty liver disease, to non-alcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma (HCC). NASH, the critical stage in NAFLD progression, is the only bridge between NAFLD and liver cirrhosis, and its persistent existence has become one of the leading causes of liver cirrhosis and even HCC. Aim of the Work To assess the value of non-invasive risk scores in differentiation between simple steatosis and NASH Patients and Methods This was prospective cohort study, conducted Internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals, on 60 patients with NAFLD divided into 2 groups: (Group I): Patients with normal liver enzymes, (Group II): Patients with persistant elevation of liver enzymes, during a period of 6 months. Results There was statistically insignificant difference between the two studied groups and sex and age. There were 12 (40%) of the group I were males and 18 (60.0%) were females. There were 16(53.3%) of the group II were males and 14(46.7%) were females. The mean age of group I was 40.63 ± 10.53 SD with range (25.0 – 59.0). The mean age of group II was 40.83 ± 9.06SD with range (27.0 – 54.0). There was statistically significant difference between the two studied groups and weight, BMI and waist circumference. There was statistically insignificant difference between the two studied groups and height, DM and HTN. There was statistically significant difference between the two studied groups and ALT, AST, GGT, ALP, ALB and Platelets. There was statistically significant difference between the two studied groups and TC, HDL, LDL, TG and AST/ALT ratio. There was statistically insignificant difference between the two studied groups and FBG. There was statistically significant difference between the two studied groups and FLI, NFS, BARD, APRI, FIB-4 and Fibrosis score. There was statistically significant difference between the two studied groups and Ultrasound (Size, Findings and Fibrosis score). The mean size in group I was 10.03 ± 1.56 SD with range (8.0 – 12.0). The mean size in group II was 13.63 ± 1.22SD with range (12.0 – 16.0). Conclusion A combination of Fibroscan, Fib-4, NFS, BARD and APRI provides a valuable non- invasive method in diagnosis of NASH patients, and this can eliminate the need for liver biopsy in patients without clear indication, BMI, platelet count, HDL cholesterol level, ALT level, and the AST/ALT ratio were independent predictors of NAFLD.

Serum dithiothreitol-oxidizing capacity (DOC) is a promising biomarker for excluding significant liver fibrosis: a proof-of-concept study

BackgroundAPRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs).MethodsDiagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations.ResultsStratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P < 0.05, P < 0.01 and P < 0.001 in 3, 1 and 3 cohort comparisons, respectively). Conversely, the DOC test was equivalent to APRI and FIB-4 when all tests showed moderate/adequate diagnostic performances (P > 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%).ConclusionsThis proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

Visceral Fat and Diabetes: Associations With Liver Fibrosis in Metabolic Dysfunction–Associated Steatotic Liver Disease

BackgroundThe prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasing globally. Noninvasive methods, such as bioelectrical impedance analysis (BIA), which measures body composition, including visceral fat, are gaining interest in evaluating MASLD patients. Our study aimed to identify factors associated with significant liver fibrosis, compare noninvasive scores, and highlight the importance of visceral fat measurement using BIA. MethodsMASLD patients seen in our OPD underwent comprehensive evaluations, including liver stiffness using transient elastography, body composition analysis using BIA, and metabolic measurements. Significant fibrosis was defined as liver stiffness measurement ≥8.2 kPa. Using multivariate analysis, we identified factors associated with significant liver fibrosis and compared four noninvasive scores with a novel DVF15 score. ResultsWe analyzed data from 609 MASLD patients seen between February 2022 and March 2023. The median age was 43 years (81% male). Among these, 78 (13%) had significant fibrosis. Patients with significant fibrosis had higher rates of type 2 diabetes (41% vs 21%, p<0.001) and elevated levels of AST, ALT, HbA1c, Fib-4, APRI, and NFS scores. They also exhibited higher visceral and subcutaneous fat. Binary logistic regression revealed type 2 diabetes and visceral fat >15% as associated with significant liver fibrosis. Additionally, the DVF15 score, combining these factors, showed a modest area under the ROC curve of 0.664 (p<0.001). ConclusionOur study identified diabetes and high visceral fat as factors associated with significant liver fibrosis in MASLD patients. We recommend that visceral fat measurement using BIA be an essential part of MASLD evaluation. The presence of either diabetes or visceral fat >15% should prompt clinicians to check for significant fibrosis in MASLD patients. Further research is warranted to validate our findings and evaluate the utility of the DVF15 score in larger cohorts and diverse populations.

Unveiling the impact of psoriasis on liver health: does methotrexate play a villainous role?

Psoriasis might bring about an increased risk of liver diseases like nonalcoholic fatty liver disease and fibrosis. The impact of methotrexate on liver function is still a cause for concern, because of the studies suggesting an increased risk of liver damage and others finding no association. The focus of this study was the liver functions in psoriatic patients investigating the impact of long-term use of methotrexate on liver in psoriasis. A retrospective investigation including 140 patients with psoriasis receiving methotrexate treatment for at least 6 months and a control group consisted of 105 healthy ones was conducted. Liver function tests (AST, ALT, PLT) were assessed, and the association of baseline PASI with FIB-4 and APRI values was investigated. Additionally, FIB-4 and APRI values at baseline, 3rd, and 6th months of methotrexate treatment for psoriasis were compared. Compared with the controls, psoriatic patients exhibited significantly higher FIB-4 scores (p = 0.004). A moderate and significant correlation was observed between baseline PASI score and baseline FIB-4 score in psoriatic patients (p < 0.001, rho = 0.626). Long-term methotrexate use had no effect on APRI or FIB-4 (p = 0.104 and p = 0.475, respectively). Psoriatic patients face an elevated risk of liver fibrosis. Long-term methotrexate use does not adversely affect liver function in psoriatic patients. Noninvasive tools like APRI and FIB-4 scores can be employed to evaluate the risk of liver disease in these patients.

Comparison of the population covered by the 2024 version of the WHO's hepatitis B prevention and treatment guidelines and the Chinese antiviral treatment guidelines

Objective: This study aims to compare the antiviral treatment similarities and differences in the population covered by the 2024 version of the World Health Organization's (WHO) hepatitis B prevention and treatment guidelines and the current Chinese hepatitis B prevention and treatment guidelines, so as to explore their impact on the indications for antiviral therapy in Chinese patients with chronic hepatitis B (CHB). Methods: The information of patients with chronic hepatitis B virus infection who did not receive antiviral treatment was collected through the registration database of the China Clinical Research Platform for Hepatitis B Elimination. Descriptive statistics were conducted on the demographic, blood, biochemical, and virological levels of patients according to the treatment recommendations of the two versions of the guidelines. The Mann-Whitney U test and χ2 test were used to compare the differences and proportional distribution of the treatment populations covered by the two guidelines. The χ2 test was used to analyze the coverage rate of different antiviral treatment indications. Results: A total of 21,134 CHB patients without antiviral treatment were enrolled. 69.4% of patients met the 2024 versions of the WHO guidelines' recommendations. 85.0% of patients met the current Chinese hepatitis B prevention and treatment guidelines. The WHO guidelines for antiviral therapy indications were met in younger patients with higher levels of ALT, AST, and APRI scores, as well as greater proportion of patients with higher viral loads (P<0.001). The WHO guidelines recommended a cut-off value of APRI>0.5, which raised the proportion of patients on antiviral therapy from 6.6% to 30.9%. 45.7% of patients met the antiviral indications for HBV DNA >2000 IU/ml with abnormal transaminase (ALT>30 U/L for males and ALT>19 U/L for females). The reduced APRI diagnostic cut-off value and ALT treatment threshold had further increased the treatment coverage rate by 91.6% in patients with chronic HBV infection in line with the 2024 versions of WHO guidelines. Conclusion: The reduction of the APRI diagnostic cut-off value and the ALT treatment threshold, based on the current hepatitis B guidelines of China, will further improve the treatment coverage of CHB patients.

Online interpretable dynamic prediction models for clinically significant posthepatectomy liver failure based on machine learning algorithms: A retrospective cohort study.

Posthepatectomy liver failure (PHLF) is the leading cause of mortality in patients undergoing hepatectomy. However, practical models for accurately predicting the risk of PHLF are lacking. This study aimed to develop precise prediction models for clinically significant PHLF. A total of 226 patients undergoing hepatectomy at a single center were recruited. The study outcome was clinically significant PHLF. Five pre- and postoperative machine learning (ML) models were developed and compared with four clinical scores, namely, the MELD, FIB-4, ALBI, and APRI scores. The robustness of the developed ML models was internally validated using 5-fold cross-validation by calculating the average of the evaluation metrics and was externally validated on an independent temporal dataset, including the area under the curve (AUC) and the area under the precision‒recall curve (AUPRC). SHapley Additive exPlanations analysis was performed to interpret the best performance model. Clinically significant PHLF was observed in 23 of 226 patients (10.2%). The variables in the preoperative model included creatinine, total bilirubin, and Child‒Pugh grade. In addition to the above factors, the extent of resection was also a key variable for the postoperative model. The pre- and postoperative artificial neural network (ANN) models exhibited excellent performance, with mean AUCs of 0.766 and 0.851, respectively, and mean AUPRC values of 0.441 and 0.645, whereas the MELD, FIB-4, ALBI, and APRI scores reached AUCs of 0.714, 0.498, 0.536 and 0.551, respectively, and AUPRC values of 0.204, 0.111, 0.128 and 0.163, respectively. In addition, the AUCs of the pre- and postoperative ANN models were 0.720 and 0.731, respectively, and the AUPRC values were 0.380 and 0.408, respectively, on the temporal dataset. Our online interpretable dynamic ML models outperformed common clinical scores and could function as a clinical decision support tool to identify patients at high risk of PHLF pre- and postoperatively.