Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear. Here, we aimed to determine if the extent of HBV DNA integration is associated with the persistence of circulating HBsAg in people exposed to HBV. We established a digital droplet quantitative inverse PCR (dd-qinvPCR) method to quantify integrated HBV DNA in patients who had been exposed to HBV (anti-HBc positive and HBeAg-negative). Total DNA extracts from both liver resections (n = 32; 14 HBsAg-negative and 18 HBsAg-positive) and fine-needle aspirates (FNA, n = 10; 2 HBsAg-negative and 8 HBsAg-positive) were analysed. Using defined in vitro samples for assay establishment, we showed that dd-qinvPCR could detect integrations within an input of <80 cells. The frequency of integrated HBV DNA in those who had undergone HBsAg loss (n = 14, mean ± SD of 1.514 × 10-3 ± 1.839 × 10-3 integrations per cell) was on average 9-fold lower than those with active HBV infection (n = 18, 1.16 × 10-2 ± 1.76 × 10-2 integrations per cell; p = 0.0179). In conclusion, we have developed and validated a highly precise, sensitive and quantitative PCR-based method for the quantification of HBV integrations in clinical samples. Natural clearance of HBV is associated with fewer viral integrations. Future studies are needed to determine if dynamics of integrated HBV DNA can inform the development of curative therapies.

Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH.

Participants with biopsy-confirmed AH and discriminant function ≥32 but Model for End-Stage Liver Disease ≤27 were randomly allocated 1:1 to receive either CAN 3 mg/kg or placebo (PBO). Liver biopsies were taken before and 28 days after treatment. The primary endpoint was the overall histological improvement in inflammation analyzed by the modified intention-to-treat principle.

Fifty-seven participants were randomized: 29 to CAN and 28 to PBO. Two participants had histology that did not corroborate the clinical diagnosis. Of the remaining 55 participants, paired histology data were evaluable from 48 participants. In CAN-treated participants, 14 (58%) of 24 demonstrated histological improvement compared with 10 (42%) of 24 in the PBO group (P = .25). There was no improvement in prognostic scores of liver function. Four (7%) of the 55 participants died within 90 days, 2 in each group. The number of serious adverse events was similar between CAN vs PBO. In post hoc exploratory analyses after adjustment for baseline prognostic factors, CAN therapy was associated with overall histological improvement (P = .04).

CAN therapy in severe AH participants with Model for End-Stage Liver Disease ≤27 did not alter biochemical or clinical outcomes compared with PBO. Nonsignificant histological improvements did not translate into clinical benefit. EudraCT, Number: 2017-003724-79; ClinicalTrials.gov, Number: NCT03775109.

Positivity for anti-gp210 and anti-centromeric antibodies (ACA) in patients with primary biliary cholangitis (PBC) have been associated with the progression of liver failure and portal hypertension (PH), respectively. The value of combining risk autoantibody assessments with prognostic scoring systems in improving risk assessment in patients with PBC remains unclear.

To investigate the prognostic significance of various combinations of anti-gp210 and ACA statuses and their enhancing the prognostic utility on the GLOBE scoring system.

Stepwise Cox regression was used to estimate the relationship between anti-gp210 antibodies or ACA and liver transplant (LT)-free survival. The GLOBE scoring system was used to stratify the patients.

A total of 1412 patients with confirmed PBC were included in the study. The anti-gp210+ status was a significant risk factor for LT/liver-related death, whereas the ACA+ status was a significant risk factor for variceal bleeding (P = 0.002 and 0.007, respectively). The anti-gp210 + ACA + status was a risk indicator for the entire cohort independent of the GLOBE score (P = 0.001, hazard ratio [HR]: 2.649, 95 % confidence interval [CI]: 1.492-4.703) and liver stiffness measurements (LSM; P = 0.039, HR: 4.969, 95 % CI: 1.088-22.692). A significant difference was observed in the area under the receiver operating characteristic curve between the fitted scoring model (consisting of the GLOBE score, anti-gp210 + ACA+ status, and albumin level) and the GLOBE scoring system alone (P = 0.034). When enrolled patients were classified as high-, medium-, and low-risk by the GLOBE scoring system (1.8 and 0.5), the anti-gp210 + ACA+ status was associated with a 1.6- and 3.3-fold higher 5-year incidence of LT/liver-related death in the high- and medium-risk groups, respectively, in comparison with the anti-gp210 + ACA- cases. The anti-gp210 + ACA+ status was also a risk indicator for the presentation of the hepatic failure phenotype in comparison with the anti-gp210- status (P = 0.007, odds ratio [OR]: 6.419, 95 % CI: 1.645-25.042), and the presentation of PH phenotype in comparison with the anti-ACA- status (OR: 3.473, 95 % CI: 1.328-9.018, P = 0.011).

The anti-gp210 + ACA+ status was an independent prognostic marker that could predict a poor prognosis in patients with PBC at diagnosis and may further optimise risk stratification in combination with the GLOBE scoring system.

This study investigated the consistency of the FIB-4, APRI, and GPR indices in assessing significant liver fibrosis and cirrhosis in patients with Coronavirus Disease 2019(COVID-19) who also suffer from various liver diseases, providing references for the clinical selection and application for non-invasive assessment methods.

The study evaluated 744 COVID-19 patients with coexisting liver diseases: 508 cases with non-alcoholic fatty liver disease (NAFLD), 158 cases with chronic hepatitis B (CHB), and 78 cases with a combination of both ailments. FIB-4, APRI, and GPR were employed to assess significant liver fibrosis and cirrhosis. Concordance among the methods was determined using Kappa analysis, and receiver operating characteristic (ROC) curves helped identify the optimal cutoff values for each index.

For COVID-19 patients with NAFLD, Kappa values for significant liver fibrosis were 0.81, 0.90, 0.80, and 0.79, and for cirrhosis, they were 0.88, 0.97,0.88, and 0.88, respectively (all p < 0.05). Among those with CHB, Kappa values were 0.81, 0.81, 0.83, and 0.75 for fibrosis, and0.87, 0.91, 0.88, and 0.92 for cirrhosis (all p < 0.05). In patients with coexisting liver diseases, the values were 0.87, 0.86, 0.86, and 0.78 for fibrosis, and 0.67, 0.69, 0.54, and 0.81for cirrhosis (all p < 0.05). Linear trend analysis revealed significant relationships between FIB-4 values, APRI values, GPR values, and the severity of COVID-19 (χ2 trend: 15.205,35.114, and 13.973, respectively, all p < 0.001), between FIB-4 values and APRI values and the coronavirus negative conversion time (all p < 0.05) in COVID-19 with NAFLD, and between FIB-4 values and GPR values and the coronavirus negative conversion time in patients with COVID-19 with CHB(all p < 0.05).

Using the current cutoff values, the non-invasive assessments demonstrated almost perfect consistency in evaluating significant liver fibrosis and cirrhosis in COVID-19 patients with liver diseases, though FIB-4 and GPR showed moderate consistency in cirrhosis evaluation in patients with coexisting liver conditions. Moreover, it also indicated that increased liver fibrosis correlates with more severe COVID-19 and prolonged coronavirus negative conversion time.

Leptin replacement therapy with metreleptin improves metabolic abnormalities in patients with generalized lipodystrophy (GLD).

Determine how timing of metreleptin initiation in the clinical course of GLD affects long-term metabolic health.

Retrospective analysis of patients ≥6 months old with congenital (n = 47) or acquired (n = 16) GLD treated with metreleptin at the National Institutes of Health since 2001. Least squares means for glycated hemoglobin (HbA1c), insulin area under the curve from oral glucose tolerance tests, triglycerides, urine protein excretion, platelets, transaminases, and aspartate aminotransferase (AST) to Platelet Ratio Index for early and late treatment groups, defined by baseline metabolic health, were analyzed during median 72 (24-108) months' follow-up.

Compared to late groups, early groups based on metabolic status had higher mean ± SEM insulin area under the curve (20 831 ± 1 vs 11 948 ± 1), lower HbA1c (5.3 ± 0.3 vs 6.8 ± 0.3%), triglycerides (101 ± 1 vs 193 ± 1 mg/dL), urine protein excretion (85 ± 1.5 vs 404 ± 1.4 mg/24 h), alanine aminotransferase (30 ± 1 vs 53 ± 1 U/L), AST (23 ± 1 vs 40 ± 1 U/L), and AST to Platelet Ratio Index (0.22 ± 1.3 vs 0.78 ± 1.3), and higher platelets (257 ± 24 vs 152 ± 28 K/µL) during follow-up (P < .05). Compared to patients ≥6 years old at baseline, patients <6 years had lower HbA1c (4.5 ± 0.5 vs 6.4 ± 0.2%) and higher AST (40 ± 1vs 23 ± 1 U/L) during follow (P < .05).

Patients with GLD who initiated metreleptin before the onset of severe metabolic complications had better long-term control of diabetes, proteinuria, and hypertriglyceridemia. Early treatment may also result is less severe progression of liver fibrosis, but further histological studies are needed to determine the effects of metreleptin therapy on liver disease.

Baseline viral replication activity influences the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B virus (HBV) infection.

To evaluate the impact of baseline viral replication activity on recurrence in HBV-related HCC after curative resection.

A multinational retrospective cohort of 2384 patients with very early or early-stage HBV-related HCC who consecutively underwent curative resection and received antiviral therapy (AVT) between 2010 and 2018 was analysed. Patients were categorised into ongoing-AVT (previously on AVT with viral suppression) and initiation-AVT (initiated AVT at the time of resection) groups. HCC recurrence was compared between these two groups based on baseline viral replication activity.

During a median follow-up of 4.9 years, 1188 (49.8%) patients developed recurrence. Multivariable analysis showed similar recurrence risk between the ongoing-AVT and initiation-AVT groups (HR, 1.09; 95% CI, 0.96-1.24). However, in cirrhotic patients, the initiation-AVT group had a higher recurrence risk than the ongoing-AVT group (HR, 1.22; 95% CI, 1.02-1.45) but not in non-cirrhotic patients (HR, 0.90; 95% CI, 0.73-1.09). Intriguingly, in the non-cirrhotic initiation-AVT group, a parabolic association was observed between baseline HBV DNA levels and the risk of recurrence, with those having 5-6 log10 IU/mL HBV DNA levels showing significantly higher recurrence risk compared to the ongoing-AVT group (HR, 1.78; 95% CI, 1.32-2.42).

The association between HBV replication activity and the risk of HCC recurrence varied depending on cirrhosis, providing important insights for optimising the timing of AVT and post-operative surveillance strategies.

Liver biopsy contribution in patients with unexplained elevation of transaminases is not clearly established. The aim was to study liver biopsy contribution in patients with unexplained elevated transaminases strictly defined according to the current guidelines, reflecting the present clinical practice.

In a retrospective study, we identified all the liver biopsies performed in patients with elevated transaminases for at least six months. Patients with a particular context, or with an identified cause of liver disease were excluded. The biopsies were classified according to the 4 following injury patterns: hepatitic, biliary, steatotic, vascular.

87 patients were included. Liver biopsy showed minimal changes or a normal histology in 48%, a steatotic pattern in 21%, a hepatitic pattern in 13%, a vascular pattern in 8%, a biliary pattern in 1%, and a mixed pattern in 8%. A cause could be determined in 21% of patients with normal histology, 85% with steatosis, 56% with hepatitis, 75% with biliary, but in none with isolated vascular pattern. Liver biopsy had important clinical and therapeutic implications in 15% of patients, with a diagnosis of autoimmune hepatitis, primary biliary cholangitis or metabolic dysfunction-associated steatohepatitis. Elevation of transaminases > 10 upper normal limit was present in all the patients with confirmed autoimmune hepatitis, but in only 7% of others.

Liver biopsy had important clinical and therapeutic implications in 15% of patients. However, the majority of patients had minimal changes without a cause, or minor vascular lesions of uncertain significance.

Antifibrotic trials rely on conventional pathology despite recognized limitations. We compared single-fiber digital image analysis with conventional pathology to quantify the antifibrotic effect of Aramchol, a stearoyl-CoA desaturase 1 inhibitor in development for metabolic dysfunction-associated steatohepatitis.

Fifty-one patients with metabolic dysfunction-associated steatohepatitis enrolled in the open-label part of the ARMOR trial received Aramchol 300 mg BID and had paired pre-post treatment liver biopsies scored by consensus among 3 hepatopathologists, and separately assessed by a digital image analysis platform (PharmaNest) that generates a continuous phenotypic Fibrosis Composite Severity (Ph-FCS) score. Fibrosis improvement was defined as: ≥1 NASH Clinical Research Network (NASH-CRN) stage reduction; "improved" by ranked pair assessment; reduction in Ph-FCS ("any" for ≥0.3 absolute reduction and "substantial" for ≥25% relative reduction). Fibrosis improved in 31% of patients (NASH-CRN), 51% (ranked pair assessment), 74.5% (any Ph-FCS reduction), and 41% (substantial Ph-FCS reduction). Most patients with stable fibrosis by NASH-CRN or ranked pair assessment had a Ph-FCS reduction (a third with substantial reduction). Fibrosis improvement increased with treatment duration: 25% for <48 weeks versus 39% for ≥48 weeks by NASH-CRN; 43% versus 61% by ranked pair assessment, mean Ph-FCS reduction -0.54 (SD: 1.22) versus -1.72 (SD: 1.02); Ph-FCS reduction (any in 54% vs. 100%, substantial in 21% vs. 65%). The antifibrotic effect of Aramchol was corroborated by reductions in liver stiffness, Pro-C3, and enhanced liver fibrosis. Changes in Ph-FCS were positively correlated with changes in liver stiffness.

Continuous fibrosis scores generated in antifibrotic trials by digital image analysis quantify antifibrotic effects with greater sensitivity and a larger dynamic range than conventional pathology.

Patients with biliary atresia (BA) suffer from progressive liver damage, even after successful Kasai portoenterostomy (KPE). The purpose of this study is to analyze the relevance of follow-up percutaneous liver biopsy (LBx) and long-term prognosis of patients with BA.

This study included patients with BA who were born between 1983 and 2005 and survived with their native liver until 10 years of age. Patient characteristics, laboratory data and Child-Pugh score at the time of LBx, and native-liver survival (NLS) and complication-free survival (CFS) in patients with mild (F0-F2) or severe fibrosis (F3, F4) on follow-up LBx were retrospectively analyzed.

Forty-three patients were gathered in this study and the most recent LBx was performed at age 21.1 ± 2.9 years. Thirty-three patients had mild fibrosis and ten patients had severe fibrosis on follow-up LBx. Long-term NLS and CFS were significantly worse in patients with severe fibrosis. Among those patients, 18 patients had follow-up LBx between the ages of 6 and 12 years, and CFS were significantly worse in patients with severe fibrosis.

We found that patients with BA with severe liver fibrosis on follow-up LBx had worse long-term survival and a higher rate of progression of complications of BA.

Given the inherent limitations of invasive biopsy and the insufficient accuracy of liver-related serum biomarkers, there is an urgent need for the development of reliable, non-invasive imaging techniques for the diagnosis of liver fibrosis. This study aims to investigate the correlation between magnetic resonance imaging (MRI) T1/T2 mapping sequences and biomarkers of collagen deposition and ongoing systemic inflammation, and to evaluate the potential of T1/T2 mapping as a non-invasive method for the accurate diagnosis of liver fibrosis.

A mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis was established and T1/T2 mapping were performed at different weeks of treatment. The histopathological analysis, collagen quantification, and inflammatory factors measurements (IL-1, IL-6, TNF-α) were conducted to correlate MRI parameters with collagen deposition and inflammation. Statistical analysis was performed using IBM SPSS Statistics (version 22.0, Chicago, IL, USA) and Origin 2018 (OriginLab Corporation, Northampton, MA, USA).

The principal findings indicated that T1 and T2 values exhibited a progressive increase with the severity of fibrosis, demonstrating a positive correlation with collagen deposition and inflammatory factors, especially the hydroxyproline content (r = 0.880, P < 0.001). The HYP content exhibited a progressive increase with advancing fibrosis stages (ρ = 0.914, P < 0.001). Similarly, T1 values increased significantly across fibrosis stage(ρ = 0.854, P < 0.001). Statistical comparison of these coefficients revealed no significant difference (Z = 1.031, P = 0.303). ROC curve analysis showed that T1 mapping was more accurate than T2 mapping in detecting collagen deposition and inflammation.

This study highlighted the potential of T1/T2 mapping as non-invasive and quantitative biomarkers for diagnosing and staging liver fibrosis, providing new insights into the onset and progression of liver fibrosis.

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

The term metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed based on a redefinition of the nonalcoholic fatty liver disease (NAFLD) criteria. Our study aimed to address the knowledge gap by comparing the diagnostic accuracy of MAFLD and NAFLD criteria in identifying significant fibrosis among patients with hepatic steatosis. A cross-sectional study was conducted on 2626 patients with hepatic steatosis treated at Beijing Ditan Hospital between January 2009 and December 2022. Patients with viral hepatitis were excluded. Significant fibrosis was defined as a Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) score F ≥ 2. MAFLD and NAFLD were diagnosed in 478 and 428 patients, respectively. Clinicopathological characteristics were compared between the MAFLD+ NAFLD- group (patients who met the criteria for MAFLD but not NAFLD) and MAFLD- NAFLD+ group (patients who met the criteria for NAFLD but not MAFLD). A total of 743 patients with histologically verified hepatic steatosis were analyzed. The MAFLD+ NAFLD- group comprised 163 (21.9%) and the MAFLD- NAFLD+ group comprised 113 (15.2%) patients. Patients in the MAFLD+ NAFLD- group were older and more likely to be male and had higher body mass index and liver stiffness levels than those in the MAFLD- NAFLD+ group. The prevalence of significant fibrosis was higher in the MAFLD+ NAFLD- group than in the MAFLD- NAFLD+ group (43.6% vs 15.9%, P < .001). The MAFLD criteria may be a better indicator of fibrosis than the NAFLD criteria. Fibrosis in patients with MAFLD can be determined by metabolic disorders, not excessive alcohol consumption.

The potential effect of ursodeoxycholic acid (UDCA) on the clinical outcomes of SARS-CoV-2 in patients with chronic liver diseases has been a subject of ongoing debate since the onset of the SARS-CoV-2 pandemic in 2019. This study aims to investigate the effect of UDCA on the prognosis of SARS-CoV-2 infection in patients with chronic liver diseases.

A total of 926 patients with chronic liver diseases who contracted their first SARS-CoV-2 infection during December 2022 to January 2023, were included in this study. Participants were divided into two groups based on the use of UDCA: the UDCA cohort (n = 329) and the non-UDCA cohort (n = 597). After performing a 1:1 age-and sex-matching, the analysis proceeded with 309 patients from each group for further evaluation.

In the UDCA-treated cohort, the incidence of asymptomatic SARS-CoV-2 infections was significantly higher, with 30.1% of patients affected, compared to 6.47% in the non-UDCA group (p < 0.0001). Multivariable analysis identified UDCA as a protective factor against symptomatic infections, yielding an odds ratio (OR) of 4.77 (95% CI: 2.70-8.44, p < 0.001). Furthermore, age over 50 was found to be a risk factor for asymptomatic infections in the UDCA cohort, with an adjusted OR of 1.51 (95% CI: 1.01-2.24, p = 0.05).

The study suggests that UDCA therapy may improve clinical outcomes in patients with chronic liver diseases patients who are infected with SARS-CoV-2, highlighting its potential role in improving prognosis within this vulnerable population. However, further research is required to validate these findings and to elucidate the mechanisms underlying UDCA's protective effect.

Biliary atresia (BA) is a severe paediatric liver disease causing cirrhosis without prompt treatment. Aspartate aminotransferase-to-platelet ratio index (APRi), a non-invasive biomarker, shows promise in assessing fibrosis and cirrhosis severity, offering an alternative to liver biopsy. However, standardised criteria and research on APRi accuracy in paediatric BA, especially across diverse populations, remain limited.

To assess the correlation between APRi values, liver fibrosis and cirrhosis severity in children with BA, evaluate APRi's diagnostic accuracy and clinical utility, and identify appropriate cut-off values for significant fibrosis and cirrhosis.

This systematic review and meta-analysis, conducted per PRISMA guidelines, evaluated non-invasive biomarkers for liver fibrosis in BA patients. Data were managed using REDCap and analysed with R software. Heterogeneity was assessed with the Cochrane Q test and I2 values.

Fourteen studies (retrospective, prospective, and one cross-sectional) examined APRi and liver fibrosis in BA. APRi cut-off values for diagnosing fibrosis and cirrhosis ranged from 0.7 to 2.26 for advanced fibrosis (F3). The meta-analysis provided pooled means and 95% confidence intervals for APRi, assessing its diagnostic performance. Significant heterogeneity was noted in studies with favourable histology, while none was observed in those with unfavourable histology, highlighting variability in APRi values.

Limited patient numbers and significant heterogeneity across studies impeded the establishment of a definitive threshold for identifying unfavourable histology in BA. Consequently, APRi's clinical utility remains unclear. Further research is required to determine its precise role as a biopsy surrogate and in clinical decision-making during BA diagnosis.

Study of diagnostic test.

IV.

To explore texture analysis' ability on T1 and T2 relaxation maps to classify liver fibrosis into no-to-mild liver fibrosis (nmF) versus severe fibrosis (sF) group using machine learning algorithms and histology as reference standard.

In this single-center study, patients undergoing 3 T MRI who also had histology examination were retrospectively enrolled. SNAPSHOT-FLASH sequence for T1 mapping, radial turbo-spin-echo sequence for T2 mapping and spin-echo echo-planar-imaging magnetic resonance elastography (MRE) sequences were analyzed. Grey-level co-occurrence matrix texture analysis features were extracted from T1 (TA-T1) and T2 (TA-T2) maps from single-slice whole-liver region-of-interest. The extracted features were evaluated as predictors for nmF and sF group classification separately using support-vector-machine algorithm combined with principal component analysis in case of texture features. Recursive Feature Elimination with Cross-Validation (RFECV) was used to identify the most significant features and the importance of selected features was assessed with permutation importance algorithm. A combined model was identified and evaluated. Area under the receiver operating characteristic curve (AUC) was used for scoring and model comparison.

46 patients (mean age 52.8 ± 16.1 years, 23 males) were evaluated. TA-T1 performed comparably to MRE (0.748 vs 0.759, p = 0.905) and T1 performed slightly worse compared to MRE which was not statistically significant (0.692 vs 0.759, p = 0.396). MRE outperformed T2 (0.759 vs 0.552) and TA-T2 (0.759 vs 0.515). RFECV algorithm identified four features: MRE, T1 and 1st two TA-T1 principal components, constituting the first combined model. The permutation importance identified T1 as feature of very low importance, therefore a second combined model was constructed, omitting T1 from the first combined model. Even though both combined models performed higher than MRE (0.759 vs 0.797, p = 0.597 for MRE vs MRE + T1 + TA-T1, and 0.759 vs 0.817, p = 0.373 for MRE vs MRE + TA-T1), it was not statistically significant.

TA-T1 performed comparably to MRE in liver fibrosis classification to nmF and sF groups, and even though not statistically significant, combining those with MRE increased the performance, suggesting their complementary nature. Given the broad availability, robustness and short scanning times of T1 mapping, we would advocate for the inclusion of T1 mapping in every clinical and research liver examination.

To explore whether T1 mapping parameters and the functional liver imaging score (FLIS) based on Gd-EOB-DTPA MRI could evaluate liver regeneration after hepatectomy for HCC patient.

This retrospective study finally included 60 HCC patients (48 men and 12 women, with a median age of 53 years). T1 relaxation time of liver before gadoxetic acid injection (T1pre) and during the hepatobiliary phase (T1HBP), reduction rate (Δ%) and FLIS were calculated, their correlations with liver fibrosis stage, hepatic steatosis, and liver regeneration, quantified as regeneration index (RI), were assessed by Kendall's tau-b correlation test or Spearman's correlation test. Multivariate linear regression analyses were used to explore the indicator of RI.

T1pre, T1HBP, Δ%, and FLIS manifested significant correlation with fibrosis stage (r = 0.434, P =0.001; r = 0.546, P < 0.001; r = -0.356, P =0.005; r = -0.653, P <0.001, respectively). T1pre showed significant correction with steatosis grade (r = 0.415, P =0.001). Fibrosis stage and steatosis grade were associated with RI (r = -0.436, P<0.001; r = -0.338, P =0.008). Accordingly, T1pre, T1HBP and FLIS were the significant predictors (P<0.05) of RI in multivariate analysis. Similarly, in the patients undergoing minor hepatectomy (n=35), T1HBP, Δ% and FLIS were related to RI (P<0.05) in multivariate analysis. Nevertheless, in the patients undergoing major hepatectomy (n=25), no T1 mapping parameter and FLIS was the independent predictor of RI.

T1 mapping parameters and FLIS were the potential noninvasive indicators of liver regeneration, except for HCC patients undergoing major hepatectomy.

The value of T1 mapping and FLIS with Gd-EOB-DTPA MRI for accurate preoperative evaluation of liver regeneration is critical to prevent liver failure and improve prognosis of HCC patients.

In recent decades, numerous non-invasive tests (NITs) for diagnosing nonalcoholic fatty liver disease (NAFLD) have been developed, however, a comprehensive comparison of their relative diagnostic accuracies is lacking. We aimed to assess and compare the diagnostic accuracy of various NITs for NAFLD using network meta-analysis (NMA).

We conducted a systematic search in seven databases up to April 2024 to identify studies evaluating the diagnostic values of NITs, with liver biopsy as the gold standard. The participants included patients with suspected or confirmed NAFLD, irrespective of age, sex, ethnicity. Statistical analysis was conducted using R 4.0.3 for Bayesian NMA and STATA 17.0 for pairwise meta-analysis. Sensitivity, specificity, diagnostic odds ratio (DOR), area under the receiver operating characteristic curve (AUC), and superiority index were calculated. Bayesian calculations were performed using the Rstan package, specifying parameters like MCMC chain count, iteration count, and operational cycles. The methodological quality of included studies was assessed using the QUADAS-2 tool.

Out of 15,877 studies, 180 were included in the quantitative synthesis, and 102 were used in head-to-head meta-analyses. For diagnosing steatosis stage 1, Hydrogen Magnetic Resonance Spectroscopy (H-MRS, DOR 15,745,657.6, 95% CI 17.2-1,014,063.59) proved to be the most accurate. For significant fibrosis, HRI leading (DOR 80.94, 95% CI 6.46-391.41), For advanced fibrosis, CK-18 showed the highest performance (DOR 102654.16, 95% CI 1.6-134,059.8). For high-risk NASH, Real-Time Elastography showing the highest performance (DOR 18.1, 95% CI 0.7-96.33). Meta-regression analyses suggested that variability in the diagnostic accuracy of NITs for NAFLD may result from differences in study design, thresholds, populations, and performance indicators.

We conducted a network meta-analysis to rank the accuracy of these tests. While some results are promising, not all NITs demonstrate substantial accuracy, highlighting the need for validation with larger datasets. Future research should concentrate on studying the thresholds of NITs and enhancing the clarity of methodological reporting.

A major histologic feature of cirrhosis is the loss of liver architecture with collapse of tissue and vascular changes per unit. We developed qVessel to quantify the arterial density (AD) in liver biopsies with chronic disease of varied etiology and stage. 46 needle liver biopsy samples with chronic hepatitis B (CHB), 48 with primary biliary cholangitis (PBC) and 43 with metabolic dysfunction-associated steatotic liver disease (MASLD) were collected at the Shuguang Hospital. The METAVIR system was used to assess stage. The second harmonic generation (SHG)/two-photon images were generated from unstained slides. Collagen proportionate area (CPA) using SHG. AD was counted using qVessel (previously trained on manually labeled vessels by stained slides (CD34/a-SMA/CK19) and developed by a decision tree algorithm). As liver fibrosis progressed from F1 to F4, we observed that both AD and CPA gradually increases among the three etiologies (P < 0.05). However, at each stage of liver fibrosis, there was no significant difference in AD or CPA between CHB and PBC compared to MASLD (P > 0.05). AD and CPA performed similar diagnostic efficacy in liver cirrhosis (P > 0.05). Using the qVessel algorithm, we discovered a significant correlation between AD, CPA and METAVIR stages in all three etiologies. This suggests that AD could underpin a novel staging system.

As an opportunistic bacterial pathogen, Klebsiella pneumoniae (KP) is prone to causing a spectrum of diseases in rabbits when their immune system is compromised, which poses a threat to rabbit breeding industry. Bacillus coagulans (BC), recognized as an effective probiotic, confers a variety of benefits including anti-inflammatory and antioxidant properties.

The purpose of this study was to investigate whether dietary BC can effectively alleviate hepatic injury caused by KP.

In this study, the rabbits were initially pretreated with varying doses of BC (1×106, 5×106, and 1×107 CFU/g), followed by a challenge with KP at a concentration of 1011 CFU/mL. Liver tissues were harvested and processed for histological assessment using H&E and VG stains to assess structural alterations. Biochemical assays were employed to quantify the enzymatic activities of T-SOD and GSH-Px, as well as the MDA content. Furthermore, ELISA was utilized to detect the levels of inflammatory cytokine (IL-10, IL-6, IL-1β and TNF-α) and apoptotic-related gene (Bcl-2, Bax).

Morphological observation indicated that BC can effectively mitigate KP-induced hepatic sinusoidal dilatation and congestion, as well as ameliorate the degree of hepatic fibrosis. Further analysis showed that BC significantly lowered MDA level in KP-treated rabbits, while enhanced the activities of T-SOD and GSH-Px. Additionally, ELISA result showed that BC pretreatment significantly reduced the levels of pro-inflammatory cytokines TNF-a, IL-6, IL-1β and pro-apoptotic gene Bax, while increasing the levels of anti-inflammatory cytokine IL-10 and anti-apoptotic gene Bcl-2 in KP-treated rabbits.

Above data indicate that BC supplementation effectively attenuated oxidative stress and inflammatory response induced by KP through augmenting the activities of antioxidant enzymes and diminishing the levels of pro-inflammatory factors. Furthermore, it reduced the Bax/Bcl-2 ratio in the liver, thereby inhibiting KP-induced apoptosis. The treatment group receiving 5x106 CFU/g BC benefitted most from the protective effect.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver-related morbidity and mortality, with hepatic steatosis being the hallmark symptom. Salvia miltiorrhiza Bunge (Smil, Dan-Shen) and Ligusticum striatum DC (Lstr, Chuan-Xiong) are commonly used to treat cardiovascular diseases and have the potential to regulate lipid metabolism. However, whether Smil/Lstr combo can be used to treat NAFLD and the mechanisms underlying its lipid-regulating properties remain unclear.

To assess the feasibility and reliability of a short-term high-fat diet (HFD) induced zebrafish model for evaluating hepatic steatosis phenotype and to investigate the liver lipid-lowering effects of Smil/Lstr, as well as its active components.

The phenotypic alterations of liver and multiple other organ systems were examined in the HFD zebrafish model using fluorescence imaging and histochemistry. The liver-specific lipid-lowering effects of Smil/Lstr combo were evaluated endogenously. The active molecules and functional mechanisms were further explored in zebrafish, human hepatocytes, and hamster models.

In 5-day HFD zebrafish, significant lipid accumulation was detected in the blood vessels and the liver, as evidenced by increased staining with Oil Red O and fluorescent lipid probes. Hepatic hypertrophy was observed in the model, along with macrovesicular steatosis. Smil/Lstr combo administration effectively restored the lipid profile and alleviated hepatic hypertrophy in the HFD zebrafish. In oleic-acid stimulated hepatocytes, Smil/Lstr combo markedly reduced lipid accumulation and cell damage. Subsequently, based on zebrafish phenotypic screening, the natural phthalide senkyunolide I (SEI) was identified as a major molecule mediating the lipid-lowering activities of Smil/Lstr combo in the liver. Moreover, SEI upregulated the expression of the lipid metabolism regulator PPARα and downregulated fatty acid translocase CD36, while a PPARα antagonist sufficiently blocked the regulatory effect of SEI on hepatic steatosis. Finally, the roles of SEI on hepatic lipid accumulation and PPARα signaling were further verified in the hamster model.

We proposed a zebrafish-based screening strategy for modulators of hepatic steatosis and discovered the regulatory roles of Smil/Lstr combo and its component SEI on liver lipid accumulation and PPARα signaling, suggesting their potential value as novel candidates for NAFLD treatment.

Children with autoimmune liver disease (AILD) may develop fibrosis-related complications necessitating a liver transplant. We hypothesize that tissue-based analysis of liver fibrosis by second harmonic generation (SHG) microscopy with artificial intelligence analysis can yield prognostic biomarkers in AILD.

Patients from single-center studies with unstained slides from clinically obtained liver biopsies at AILD diagnosis were identified. Baseline demographics and liver biochemistries at diagnosis and 1 year were collected. Clinical endpoints studied included the presence of varices, variceal bleeding, ascites, HE, and liver transplant. In collaboration with HistoIndex, unstained slides underwent SHG/artificial intelligence analysis to map fibrosis according to 10 quantitative fibrosis parameters based on tissue location, including total, periportal, perisinusoidal, and pericentral area and length of strings.

Sixty-three patients with AIH (51%), primary sclerosing cholangitis (30%), or autoimmune sclerosing cholangitis (19%) at a median of 14 years old (range: 3-24) were included. An unsupervised analysis of quantitative fibrosis parameters representing total and portal fibrosis identified a patient cluster with more primary sclerosing cholangitis/autoimmune sclerosing cholangitis. This group had more fibrosis at diagnosis by METAVIR classification of histopathological review of biopsies (2.5 vs. 2; p = 0.006). This quantitative fibrosis pattern also predicted abnormal 12-month ALT with an OR of 3.6 (1.3-10, p = 0.014), liver complications with an HR of 3.2 (1.3-7.9, p = 0.01), and liver transplantation with an HR of 20.1 (3-135.7, p = 0.002).

The application of SHG/artificial intelligence algorithms in pediatric-onset AILD provides improved insight into liver histopathology through fibrosis mapping. SHG allows objective identification of patients with biliary tract involvement, which may be associated with a higher risk for refractory disease.

Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease.

We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests.

Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data are available. We aimed to (i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; and (ii) assess whether liver (LSM) and spleen stiffness measurements could diagnose PSVD and predict postoperative complications. This is a prospective single-center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient, we evaluated previous exposure to chemotherapy, comorbidities, elastography, type of surgery, histological features at the resection specimen, morbidity (post-hepatectomy liver failure and major complications according to Clavien-Dindo), and 90-day survival. Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. Spleen stiffness measurements <21 kPa (negative predictive value 87%) and >40 kPa (positive predictive value 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of post-hepatectomy liver failure (22% vs. 45%) and major complications (11% vs. 31%). Preoperative LSM was associated with postoperative morbidity. The cutoff LSMs <4.5 and >8 kPa predicted the risk of clinically significant post-hepatectomy liver failure (0%, 11%, and 33% in LSM <4.5, 4.5-8, and >8 kPa, respectively) and major complications (0%, 25%, 44% in LSM <4.5, 4.5-8, and >8 kPa, respectively). PSVD is very common among patients undergoing liver surgery for metastases, and it is associated with increased morbidity. LSM and spleen stiffness measurements can correctly identify patients with PSVD and those at risk of clinically relevant postoperative complications.

This retrospective study was conducted to investigate the diagnostic accuracy of ultrasound-derived fat fraction (UDFF) for grading hepatic steatosis using liver histology as the reference standard.

Seventy-three patients with liver disease were assessed using UDFF and liver biopsy. Pearson's test and the Bland-Altman plot were used to assess the correlation between UDFF and histological fat content in liver sections. The UDFF cutoff values for histologically proven steatosis grades were determined using the area under the receiver operating characteristic curve (AUROC).

The median age of the patients was 66 (interquartile range 54-74) years, and 33 (45%) were females. The UDFF values showed a stepwise increase with increasing steatosis grade (p < .001) and were strongly correlated with the histological fat content (r = .7736, p < .001). The Bland-Altman plot revealed a mean bias of 2.384% (95% limit of agreement, - 6.582 to 11.351%) between them. Univariate regression analysis revealed no significant predictors of divergence. The AUROCs for distinguishing steatosis grades of ≥ 1, ≥2, and 3 were 0.956 (95% confidence interval [CI], 0.910-1.00), 0.926 (95% CI, 0.860-0.993), and 0.971 (95% CI, 0.929-1.000), respectively. The UDFF cutoff value of > 6% had a sensitivity and specificity of 94.8% and 82.3%, respectively, for diagnosing steatosis grade ≥ 1. There was no association between UDFF and the fibrosis stage.

UDFF shows strong agreement with the histological fat content and excellent diagnostic accuracy for grading steatosis. UDFF is a promising tool for detecting and quantifying hepatic steatosis in clinical practice.

Direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) infection offer an opportunity to eliminate the disease. This study aimed to identify and relink to care HCV patients previously lost to medical follow-up in the health area of Pontevedra and O Salnés (Spain) using an artificial intelligence-assisted system.

Active retrospective search of previously diagnosed HCV cases recorded in the Galician Health Service proprietary health information exchange database using the Herramientas para la EXplotación de la INformación (HEXIN) application.

Out of 99 lost patients identified, 64 (64.6%) were retrieved. Of these, 62 (96.88%) initiated DAA treatment and 54 patients (87.1%) achieved a sustained virological response. Mean time from HCV diagnosis was over 10 years. Main reasons for loss to follow-up were fear of possible adverse effects of treatment (30%) and mobility impediments (21%). Among the retrieved patients, almost one in three presented advanced liver fibrosis (F3) or cirrhosis (F4) at evaluation. In sum, HCV patients lost to follow-up can be retrieved by screening past laboratory records. This strategy promotes the achievement of HCV elimination goals.

The determinants of hepatitis C virus (HCV) viral load remain incompletely understood and may differ in females, who are relatively protected from the consequences of HCV infection during their reproductive years. We aimed to evaluate how age affects the relationship between sex and viral load. n = 922 patients (males n = 497, median age 62 years), all naïve to direct antiviral agents, were studied. Females were older (median age 68 vs. 57, p < 0.001) and had a higher prevalence of genotype 2 (33% vs. 20%, p < 0.001) than males; there was no difference between sexes regarding the METAVIR stage. The median HCV RNA concentration was 1.017 × 106 IU/mL (interquartile range, 0.286-2.400). Among males, the METAVIR stage was the strongest independent predictor of a high viral load (defined as the highest two quartiles), with advanced stages inversely associated with viral load (p = 0.008). In females, age was the only independent predictor, with women aged ≥55 years exhibiting higher loads (p = 0.009). These findings are consistent with data showing that estrogens exert an antiviral effect in in vitro models of HCV. Their declining levels after the menopause may explain the "catch-up" phase of HCV-related liver disease, observed in older women.

Metabolic syndrome (MetS) is driven by a complex interplay of genetic, lifestyle, and dietary factors, leading to weight gain, insulin resistance, dyslipidemia, and chronic inflammation. Gut microbiota dysbiosis has been recently recognized as a key contributor to MetS, leading to advancements in gut microbiome-based interventions to improve health outcomes. Considering the unique challenges associated with the use of pre/probiotics, short-chain fatty acids (SCFA), also known as postbiotics, have emerged as promising therapeutic agents due to their role in modulating host metabolism and physiology. Considering this, the aim of the current study was to explore the therapeutic potential of SCFA (butyrate, propionate, and acetate) supplementation against a high-fat diet (HFD)-induced experimental model of MetS in male Wistar rats. Alterations in body weight, lipid profile, histopathology, and adipose tissue accumulation were assessed to establish SCFA-mediated amelioration of experimental MetS. Further, the enzymatic (GPx, Catalase, GR, and GST) and non-enzymatic (LPO, total ROS, and Redox ratio were evaluated. The results indicated that SCFA supplementation could effectively mitigate key features of MetS. A significant reduction in body weight gain and fasting blood glucose levels, along with markedly lowered triglycerides, total cholesterol, and LDL levels, with partial restoration of HDL levels was observed following SCFA supplementation. SCFA administration also attenuated MetS-associated hepatic damage as studied by histopathological investigation and analysis of liver function marker enzyme activities. Such ameliorative effects of SCFA against HFD-induced MetS were owed to potential redox modulation studied using enzymatic and non-enzymatic oxidative stress markers. In conclusion, the study's outcomes show that SCFA supplementation could potentially be used against managing MetS. It underscores the therapeutic potential of SCFA by placing them as a novel gut microbiome-based dietary approach to improve metabolic health and reduce the risk of MetS-associated complications. However, more detailed mechanistic explorations are warranted in the future, leading to their beneficial role in MetS contributing to holistic health outcomes.

Wilson's disease (WD) is caused by mutations in the ATP7B gene, resulting in copper accumulation and toxicity in liver and brain tissues. Due to the initial asymptomatic liver involvement, the progression of liver injuries in WD stays primarily unknown. Atp7b-/- knockout mice have been shown to be an appropriate model of WD for liver involvement.

A total of 138 Atp7b-/- mice were included and separated into five groups according to age as follows: 6, 20, 39 and 50 weeks without treatment, and 50 weeks with copper chelator treatment from 39 to 50 weeks of age and compared with 101 wild-type (WT) mice at the same stages. The evolution of histological liver lesions was analysed and compared between groups.

Significant changes were observed in Atp7b-/- mice compared with WT. Copper deposits in hepatocytes appeared as early as 6 weeks but no significant increase over time was observed. Inflammation appeared as early as 6 weeks and progressed henceforth. Lobular and periportal acidophilic bodies appeared after 20 weeks. Significant atypia was also observed at 20 weeks and increased over time to reach a severe stage at 39 weeks. Fibrosis also became apparent at 20 weeks, progressing subsequently to precirrhotic stages at 50 weeks. Copper content, inflammation and fibrosis scores were significantly reduced in the treated group. No bile duct lesions or dysplastic changes were noted.

Copper accumulation leads to progressive changes in Atp7b-/- mice regarding inflammation, fibrosis and atypia. The severity of liver damage is lessened by chelation therapy.

In the absence of physiological mechanisms to excrete excessive iron, the administration of iron chelation therapy is necessary. Age and hormones have an impact on the absorption, distribution, metabolism, and excretion of the medications used to treat iron excess, resulting in notable sex- and gender-related variances.

Here, we aimed to review the literature on sex and gender in iron overload assessment and treatment.

The development of iron chelators has shown to be a successful therapy for lowering the body's iron levels and averting the tissue damage and organ failure that follows. Numerous studies have described how individual factors can impact chelation treatment, potentially impact therapeutic response, and/or result in inadequate chelation or elevated toxicity; however, most of these data have not considered male and female patients as different groups, and particularly, the effect of hormonal variations in women have never been considered.

An effective iron chelation treatment should take into account sex and gender differences.

Long-term outcomes of using HCV-positive donors in HCV-negative recipients in liver transplantation (LT) are not well established. Data from the United Network for Organ Sharing (UNOS) database between July 1, 2015, and December 31, 2023, were analyzed. The cohort included 44,447 HCV antibody-negative (Ab-) candidates who underwent deceased donor LT. Changes in case numbers and utilization rates of HCV-positive donors, divided into HCV-viremic (NAT+) or Ab+ nonviremic (Ab+/NAT-), were assessed. Kaplan-Meier analysis and propensity score matching were used to evaluate 5-year graft survival. The number of HCV-viremic donation after brain death (DBD) donors and their use in LT for HCV Ab- recipients peaked at 640 donors in 2019 and 289 LTs in 2022. In contrast, Ab+ nonviremic DBD donations are rising, with 536 donors and 284 LTs in 2023. The utilization rate of viremic DBD grafts has continuously decreased despite increased willingness by waitlist candidates to accept them. HCV-positive donation after circulatory death donors were seldom utilized in the study period. The 5-year graft survival rates for HCV-viremic, Ab+ nonviremic, and naïve donors were not significantly different in either DBD ( p = 0.56) or donation after circulatory death ( p = 0.52). Furthermore, Ishak stage 2 or 3 fibrotic DBD grafts had similar 5-year graft survival to nonfibrotic grafts. The findings suggest that the long-term outcome of using HCV-viremic DBD or donation after circulatory death grafts for HCV-negative recipients is comparable to that of other graft types and that fibrotic grafts have the potential to expand the DBD donor pool.

To evaluate the diagnostic value of the FibroScan-AST (FAST) score, non-alcoholic fatty liver fibrosis score (NFS), FibroScan, and liver fibrosis index (FIB-4) for identifying fibrotic non-alcoholic steatohepatitis (NASH) in patients with chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD).

All patients with CHB and MAFLD who underwent liver biopsy at the Zhenjiang Third Hospital affiliated with Jiangsu University between August 2010 and December 2022 were included in the analysis. The diagnostic accuracy of FAST, NFS, FibroScan, and FIB-4 for diagnosing NASH and liver fibrosis were evaluated based on the area under the receiver-operating characteristic curve (AUC).

A total of 156 patients with CHB combined with MAFLD were included, including 69 with NASH and fibrosis stage 2 or higher (NASH+F ≥ 2), and 16 with NASH and cirrhosis (NASH+F4). The AUC of FAST, NFS, liver stiffness measurement (LSM), and FIB-4 for diagnosing NASH+F ≥ 2 was 0.739 (p < 0.001), 0.643 (p = 0.006), 0.754 (p < 0.001), and 0.665 (p = 0.003), respectively. The specificity of FAST, NFS, LSM, and FIB-4 was 67%, 51.8%, 78.6% and 76.8%, respectively, and the sensitivity was 75%, 78.6%, 67.9%, and 53.6%, respectively. No significant differences were found between groups. The AUC of FAST, NFS, LSM, and FIB-4 for diagnosing NASH+F4 was 0.650 (p = 0.038), 0.725 (p = 0.001), 0.851 (p < 0.001), and 0.560 (p = 0.533), respectively. The specificity of the FAST, NFS, LSM, and FIB-4 was 55.9%, 50.0%, 71.6%, and 75.5%, respectively and the sensitivity was 80.0%, 100%, 100%, and 50.0%, respectively. The differences between AUCs of FIB-4 and FAST compared with LSM were 0.291 and 0.201, respectively (p < 0.05).

In patients with CHB combined with MAFLD, FAST did not have better accuracy than NFS and FIB-4 for predicting fibrotic NASH, whereas LSM had better accuracy than FAST and FIB-4.