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Type 2 diabetes (T2D) is a risk for advanced fibrosis (AF) in patients with nonalcoholic fatty liver disease (NAFLD). Recent data suggest that commonly used fibrosis scores (NAFLD fibrosis score [NFS], aspartate to alanine aminotransferase ratio [AST/ALT], AST to platelet ratio index, and Fibrosis-4) may have low sensitivity and negative predictive value to detect AF in patients with diabetes.1,2 The aim of this study was to develop a simple noninvasive fibrosis score to detect AF in patients with diabetes and compare its performance with other fibrosis scores.

Introduction In subjects with nonalcoholic fatty liver disease (NAFLD), advanced fibrosis (AF) carries the highest risk of adverse liver-related events. To reduce the number of unnecessary biopsies, several noninvasive tools (NITs) for the risk stratification of fibrosis have been developed. We conducted this meta-analysis to assess the performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis scores (NFS), the 2 most common NITs, for the appropriate selection of subjects with AF for biopsy. Methods Four databases were searched until December 2020 (CRD42021224766). Original articles reporting data on the performance of FIB-4 and NFS, interpreted according to standard cutoffs in subjects with biopsy-proven NAFLD, were included. Separate data extractions were performed according to the lower cutoff, the higher cutoff, and the dual threshold approach. The numbers of subjects classified as true-negative, true-positive, false-negative, and false-positive were extracted. Summary operating points were estimated using a random-effects model. Results Eighteen studies evaluating 12,604 subjects were included. Participants were adult outpatients with biopsy-proven NAFLD or nonalcoholic steatohepatitis. Overall, a weak-to-moderate performance was found for both scores. The head-to-head comparison showed FIB-4 to be associated with a higher performance in ruling in and NFS in ruling out AF in the single threshold approach, whereas, with the dual threshold approach, a lower prevalence of indeterminate findings was found for FIB-4. Discussion This meta-analysis suggested that currently available NITs have a limited performance in identifying AF among subjects with NAFLD. Further studies are needed to optimize existing thresholds or develop new NITs.

Background and Aim The Gut and Obesity in Asia Workgroup recently reported that a two‐step approach using fibrosis scores followed by liver stiffness measurement (LSM) could accurately detect patients with non‐alcoholic fatty liver disease (NAFLD) having advanced fibrosis in low‐risk fibrosis populations. This study aimed to validate the utility of this approach using a Japanese health checkup registry. Methods This cross‐sectional study included subjects who underwent a health checkup from 2014 to 2019. Using estimated fibrosis stage measured by LSM as a standard, we calculated the percentage of misclassification from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis‐4 score [FIB‐4]) and LSM, alone or in combination. Results Of 630 subjects with NAFLD, 4 (0.8%) had advanced fibrosis. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. This approach was associated with a high specificity of approximately 100% and a negative predictive value of 99.7%. The percentage of misclassification based on NFS or FIB‐4 values followed by LSM in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively. In addition, very few false negatives occurred for both NFS and FIB‐4. Conclusion The two‐step approach helps to identify the subjects with NAFLD who have advanced fibrosis during a routine health checkup and is associated with only a few false negatives., We validated “two step approach” using health checkup subjects with nonalcoholic fatty liver disease. In the first‐step evaluation, only 21.4–38.0% of subjects needed further testing. The percentage of misclassification based on NAFLD fibrosis score (NFS) or Fibrosis‐4 score (FIB‐4) values followed by liver stiffness measurement (LSM) in all subjects and using LSM after NFS or FIB‐4 determination only in subjects with indeterminate/high NFS or FIB‐4 values (two‐step approach) was 0% and 0.3% and 0.16% and 0.3%, respectively.

Background and Aims Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. Methods A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. Results Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004–5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083–9.725, p

BACKGROUND The utility of noninvasive tests (NITs) for the diagnosis of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is limited by indeterminate results and modest predictive values (PVs). Algorithms of sequential NITs may overcome these shortcomings. Thus, we sought to systematically review the accuracy of sequential algorithms for assessing advanced fibrosis in NAFLD. METHODS A systematic review was performed following guidelines in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. A literature search of PubMed and Embase was performed in July of 2020 to identify studies that evaluated diagnostic characteristics of sequential NIT algorithms in NAFLD. RESULTS Among 8 studies meeting inclusion criteria, 48 algorithms were studied in 6741 patients. The average sensitivity, specificity, positive PV, negative PV, and proportion of indeterminate values for included algorithms were 72%, 92%, 88%, 82%, and 25%, respectively. Six algorithms achieved sensitivities in the top quartile (≥86.3%) with

The increasing burden of non-alcoholic fatty liver disease means that robust clinical pathways need to be established in primary care to identify patients with advanced fibrosis who may benefit from specialist management. This article summarises the current landscape of non-invasive liver fibrosis tests and discusses the outcomes and lessons learned from non-alcoholic fatty liver disease pathways that have been instigated around the UK. The inherent challenges of implementing such pathways are explored, along with developing technologies, such as artificial intelligence blood testing, which will likely play an important role in helping to identify and risk-stratify more patients with non-alcoholic fatty liver disease in primary care in the future.

Background and Aim Advanced fibrosis is the most important predictor of liver‐related mortality in non‐alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting. Methods We enrolled and reviewed 122 biopsy‐proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3–4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST‐to‐platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis‐4 (FIB‐4) score, and NAFLD fibrosis score. Results FIB‐4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB‐4 score, The aim of this study was to compare the diagnostic performance of non‐invasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy in the management of NAFLD in a primary care setting. FIB‐4 score outperforms other scoring systems based on AUROC and NPV. Further stratification of the patients within the indeterminate group by other clinical predictors of NASH such as abnormal GGT level and presence diabetes mellitus (DM) could further reduce the number of patients who are unlikely to have advanced fibrosis by 52% and 35% for DM, respectively.

There has been an increased interest in the use of noninvasive tests (NITs) to identify advanced liver fibrosis in patients with nonalcoholic fatty liver disease (NALFD). The aim of our study was to define the change in tests’ characteristics (sensitivity and specificity) of different combinations of NITs to detect advanced fibrosis in NAFLD. We stratified NITs into first and second tiers and compared two different strategies of combining NITs to screen for advanced fibrosis in patients with NAFLD. One strategy was using NITs in parallel, and the other was using NITs sequentially. Within both of these strategies, there were two ways of interpreting the overall results. The first way was called “the AND rule,” where a positive result required both individual test results to be positive. The second way was called “the OR rule,” where a positive result required only one individual test to be positive. Accuracy of NITs was obtained from the literature search. Combined accuracy and likelihood ratio (LR) were calculated. Combination testing with parallel and sequential order testing under the AND Rule resulted in overall higher specificity and LR+ then using the NITs alone. Specificity ranged from 0.91 to 0.99, and LR+ from 9.3 to 68.6. The subsequent use of MRE was associated with LR+ between 36 and 69. Sensitivity was higher with parallel and sequential order testing under the OR Rule. LR+ ranged from 1.4 to 7.5, and sensitivity from 0.82 to 0.98. Screening for advanced fibrosis should be performed sequentially, with positive results confirmed by additional testing. Specificity and LR+ were highest when MRE was employed as the confirmatory test.

Background The prevalence of nonalcoholic fatty liver disease (NAFLD) is significantly rising worldwide. Type-2 diabetes (T2D) is a major risk factor for NAFLD progression. Aim To assess the association of commonly used medications to advanced fibrosis (AF) in patients with biopsy-proven NAFLD and T2D. Methods We used the International Classification of Disease 9th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF. Results A total of 1183 patients were included in the final analysis, out of which 32% (n = 381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females (65%) and Caucasians (85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF. Conclusion In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

BACKGROUND Updated prevalence and outcome data for nonobese NAFLD for the multi-ethnic US population is limited. OBJECTIVES We aimed to investigate the prevalence, clinical characteristics and mortality of obese and nonobese individuals with NAFLD in the United Sates. METHODS A retrospective study was conducted using the 1999-2016 NHANES databases. We determined hazard ratio stratified by obesity status in NAFLD individuals using Cox regression and log-rank test. RESULTS Overall NAFLD prevalence was 32.3%: 22.7% were obese and 9.6% were nonobese, with increasing trend over time for obese NAFLD, but not nonobese NAFLD. Amongst those with NAFLD, 29.7% (95% CI: 27.8%-31.7%) were nonobese, of which 13.6% had lean NAFLD. Nonobese NAFLD was more common in older (40.9% if ≥ 65 vs. 24.2% if

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)., The term metabolic-associated fatty liver disease (MAFLD) has been proposed to define positively fatty liver disease in the form associated with metabolic risk factors. The aim of this study was to assess the dietary intake of MAFLD and explore a possible relationship between its inflammatory characteristics (assessed by Dietary Inflammatory Index-DII®), the degree of liver fibrosis (assessed by transient elastography), and the amount of alcohol intake. MAFLD patients were included (n = 161) and were classified, according to the amount of alcoholic intake, as MAFLD without alcohol intake (n = 77) and MAFLD with alcohol intake (n = 84), with 19 presenting harmful alcoholic consumption. Dietary intake was 1868 ± 415 kcal/day and did not present differences in energy or nutrient intake based on the presence of metabolic comorbidities. Patients with MAFLD and alcohol intake consumed significantly more energy and presented a tendency for higher intake of carbohydrates and sugar. Patients with harmful alcohol intake presented a higher intake of total fat and cholesterol compared with moderate alcohol intake. There were no differences in DII® based on fibrosis severity or the amount of alcohol consumption. This work contributes to the characterization of baseline dietary intake in MAFLD patients, paving the way to design more suited dietary interventional trials.

International audience; Background: The epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) in diabetes have been mainly investigated in the hospital setting. The goal of this study was to evaluate the characteristics of NAFLD and its impact on morbidity and mortality in type 2 diabetic subjects in a community setting. Method: This study included 199 341 participants in the nationwide Constances cohort. After patients with excessive alcohol consumption, viral hepatitis or other causes of liver disease were excluded, 164 285 were analysed and 8386 (5.3%) were considered to have type 2 diabetes. The non-invasive diagnosis of NAFLD and advanced fibrosis was made using a combination of the fatty liver index and Forns index. Median follow-up was 2.5 years. Results: Diabetes increased the risk of NAFLD by sixfold (adjusted OR 6.05, 95% CI 5.68-6.45) and the risk of advanced fibrosis by 3.76-fold (aOR 3.76, 95% CI 2.87-4.91) in NAFLD subjects. After controlling for confounders, the presence of NAFLD in diabetic subjects was associated with an increased risk of severe liver-related events (aHR 2.53, 95% CI 1.36-4.69), cardiovascular disease (CVD, aHR 2.71, 95% CI 1.72-4.26) and overall mortality (aHR 2.91, 95% CI 1.53-5.53). The risk of hepatic and extrahepatic complications in diabetic subjects with NAFLD significantly increased with the severity of fibrosis (P

One fifth of patients with nonalcoholic fatty liver disease (NAFLD) may progress to nonalcoholic steatohepatitis (NASH), which can increase the risk of cirrhosis, cancer, and death. To date, reported predictors of NASH progression have been heterogeneous. We identified determinants of fibrosis progression in patients with NASH in the United States using physician-reported data from the real-world Global Assessment of the Impact of NASH (GAIN) study, including demographics and clinical characteristics, NASH diagnostic information, fibrosis stage, comorbidities, and treatment. We developed a logistic regression model to assess the likelihood of fibrosis progression since diagnosis, controlling for sociodemographic and clinical variables. An iterative nested model selection approach using likelihood ratio test determined the final model. A total of 989 patients from the GAIN US cohort were included; 46% were women, 58% had biopsy-proven NAFLD, and 74% had fibrosis stage F0–F2 at diagnosis. The final multivariable model included age, years since diagnosis, sex, employment status, smoking status, obesity, fibrosis stage, diagnostic biopsy, Vitamin E, and liver transplant proposed at diagnosis. Odds of progression were 17% higher (odds ratio, 1.17 [95% CI: 1.11–1.23]; P < .001) with each year since NASH diagnosis, 41% lower (0.59 [0.38–0.90]; P = .016) for women than men, 131% higher (2.31 [1.30–4.03]; P = .004) for smokers versus non-smokers, and 89% higher (1.89 [1.26–2.86]; P = .002) with obesity. Odds of progression were also higher with part-time, retired, unemployed, and unable to work due to NASH status versus full-time employment, and when a liver transplant was proposed at diagnosis. Disease duration and severity, obesity, smoking, and lack of full-time employment were significant determinants of fibrosis progression. These findings can support clinical and health-policy decisions to improve NASH management in the US.

One fifth of patients with nonalcoholic fatty liver disease (NAFLD) may progress to nonalcoholic steatohepatitis (NASH), which can increase the risk of cirrhosis, cancer, and death. To date, reported predictors of NASH progression have been heterogeneous. We identified determinants of fibrosis progression in patients with NASH in the United States using physician-reported data from the real-world Global Assessment of the Impact of NASH (GAIN) study, including demographics and clinical characteristics, NASH diagnostic information, fibrosis stage, comorbidities, and treatment. We developed a logistic regression model to assess the likelihood of fibrosis progression since diagnosis, controlling for sociodemographic and clinical variables. An iterative nested model selection approach using likelihood ratio test determined the final model. A total of 989 patients from the GAIN US cohort were included; 46% were women, 58% had biopsy-proven NAFLD, and 74% had fibrosis stage F0–F2 at diagnosis. The final multivariable model included age, years since diagnosis, sex, employment status, smoking status, obesity, fibrosis stage, diagnostic biopsy, Vitamin E, and liver transplant proposed at diagnosis. Odds of progression were 17% higher (odds ratio, 1.17 [95% CI: 1.11–1.23]; P

Hepatitis C virus (HCV) is a major risk factor for hepatocellular carcinoma (HCC), one of the deadliest cancers with increasing incidence over the past few decades (1). Direct-acting antiviral (DAA) therapy in HCV-infected patients has been shown to lower the risk of liver-related events, including HCC (2). Despite sustained virological responses (SVR >95%), the risk of developing HCC in DAA-treated HCV patients with advanced fibrosis or cirrhosis remains high at 0.3 to 1.8% per year (3). On a molecular level, persistent epigenetic changes despite DAA cure are associated with hepatic carcinogenesis (4). Current AASLD-IDSA (5) and EASL (6) guidelines recommend lifelong surveillance for HCV-cured patients with cirrhosis; therefore, a more precise identification of clinical and molecular markers associated with HCC risk among these patients will have significant cost-effectiveness and resource utilization implications.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiovascular disease. It is not well understood, however, which individuals with NAFLD are at highest risk for cardiovascular disease. AIMS To determine the factors associated with incident cardiovascular events in a prospective cohort of individuals with biopsy-proven NAFLD without pre-existing cardiovascular disease. METHODS From 2011 to 2018, adults with biopsy-proven NAFLD without cardiovascular disease were enrolled in a tissue repository and were followed prospectively to the first recorded date of incident cardiovascular disease, death or the end of follow-up (11/1/2018). Competing risks analysis was performed to identify predictors of incident cardiovascular disease. RESULTS After a median follow-up time of 5.2 years, 26/285 (9.1%) individuals experienced an incident cardiovascular event. Advanced fibrosis (stage 3-4) on biopsy was a significant predictor of incident cardiovascular disease, and this persisted on multivariable analysis (SHR 2.86, 95% CI 1.36-6.04) after considering relevant covariates, including cardiovascular risk scores, which were not independent predictors. Of the non-invasive indicators of fibrosis, the NAFLD fibrosis score was the only independent predictor of cardiovascular disease. Other histologic features, including steatohepatitis, were not associated with incident cardiovascular disease. CONCLUSIONS In adults with biopsy-proven NAFLD, advanced fibrosis on biopsy and higher NAFLD fibrosis score were significant and independent predictors of incident cardiovascular disease, even after considering traditional risk factors and cardiovascular risk scores. These findings should be considered when evaluating NAFLD patients for primary prevention of cardiovascular disease, and further evaluation into the link between advanced fibrosis and cardiovascular disease is needed.

Sarcopenia is common in patients with advanced fibrosis or cirrhosis. We investigated the correlation between sarcopenia and other clinical variables, in particular, significant liver fibrosis in patients with chronic liver diseases (CLDs).Patients with CLDs who underwent transient elastography (TE) and bioelectrical impedance analysis between 2015 and 2017 were retrospectively recruited. The sarcopenia index (SI) was calculated as follows: SI = total appendicular skeletal muscle mass (kg)/ body mass index (BMI) (kg/m). Sarcopenia was defined as SI less than 0.789 for men and less than 0.521 for women. Significant liver fibrosis and fatty liver were defined using TE liver stiffness value more than 7 kPa and controlled attenuation parameter more than 250 dB/m, respectively.Of 2168 patients recruited, 218 (10.1%) had sarcopenia. Age, BMI, diabetes, hypertension, fasting glucose, aspartate aminotransferase, and liver stiffness value were correlated positively with sarcopenia (all P 0.05), whereas male sex, viral etiology, obesity (BMI 25 kg/m), total bilirubin, and serum albumin were correlated negatively with sarcopenia (all P 0.05). On multivariate analysis, TE-defined significant liver fibrosis was associated independently with sarcopenia (odds ratio = 1.597; 95% confidence interval: 1.174-2.172; P = 0.003), together with age, male sex, viral etiology, and TE-defined fatty liver (all P 0.05). Among the subgroups with ultrasonography-defined nonalcoholic fatty liver disease (n = 957), sarcopenia was also associated independently with TE-defined significant liver fibrosis (odds ratio = 1.887; 95% confidence interval: 1.261-2.823; P 0.001).Sarcopenia is associated independently with significant liver fibrosis in patients with CLDs. Further studies are required to determine whether interventions to improve muscle mass can improve liver fibrosis.

Background: New direct-acting antiviral drugs can eradicate hepatitis C virus (HCV) infection in over 90% of patients and can even reduce the risk of complications in advanced fibrosis/cirr...

Kaya, Eda/0000-0002-9293-2811; Demirtas, Coskun/0000-0002-0004-2740; Keklikkiran, Caglayan/0000-0001-6304-5554; Yilmaz, Yusuf/0000-0003-4518-5283; BAKIR, Alev/0000-0003-0664-5822 WOS:000550767400012 PubMed ID: 31530739 Background/Aims: Advanced fibrosis (F >= 3) indicates poor outcomes in nonalcoholic fatty liver disease (NAFLD). Here, we examined the diagnostic performance of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) for detecting (or excluding) advanced fibrosis in patients with biopsy-proven NAFLD. Methods The diagnostic performance of each non-invasive test according to previously identified cutoff points indicating low and high risk for advanced fibrosis was determined in 463 patients with NAFLD. Patients who scored 2.67 on the FIB-4 were considered at low and high risk for advanced fibrosis, respectively. Patients who scored 0.676 on the NFS were considered at low and high risk for advanced fibrosis, respectively. Results: Eighty-one patients (17.5%) had biopsy-proven advanced fibrosis (F >= 3). The published FIB-4 cutoff values for low and high risk were able to exclude advanced fibrosis with negative predictive values (NPVs) of 0.907 and 0.843 and specificities of 74% and 97%, respectively. The published NFS cutoff values for low and high risk were able to exclude advanced fibrosis with NPVs of 0.913 and 0.842 and specificities of 63% and 96%, respectively. If biopsies were performed in only patients with a FIB-4 above the low cutoff point (>= 1.3), 67.1% could be avoided. Conversely, if biopsies were performed in only patients with an NFS above the low cutoff point (>=-1.455), 57.0% could be avoided. Conclusions: The main clinical utility of the FIB-4 and NFS in patients with NAFLD lies in the ability to exclude, not identify, advanced fibrosis.

Objectives The aim of this study is to develop an intelligent diagnostic system utilizing machine learning for data cleansing, then build an intelligent model and obtain new cutoff values for APRI (aspartate aminotransferase-to-platelet ratio) and FIB-4 (fibrosis score) for the prediction and staging of fibrosis in children with chronic hepatitis C (CHC). Methods Random forest (RF) was utilized in this study for data cleansing; then, prediction and staging of fibrosis, APRI and FIB-4 scores and their areas under the ROC curve (AUC) have been obtained on the cleaned dataset. A cohort of 166 Egyptian children with CHC was studied. Results RF, APRI, and FIB-4 achieved high AUCs; where APRI had AUCs of 0.78, 0.816, and 0.77; FIB-4 had AUCs of 0.74, 0.828, and 0.78; and RF had AUCs of 0.903, 0.894, and 0.822, for the prediction of any type of fibrosis, advanced fibrosis, and differentiating between mild and advanced fibrosis, respectively. Conclusions Machine learning is a valuable addition to non-invasive methods of liver fibrosis prediction and staging in pediatrics. Furthermore, the obtained cutoff values for APRI and FIB-4 showed good performance and are consistent with some previously obtained cutoff values. There was some agreement between the predictions of RF, APRI and FIB-4 for the prediction and staging of fibrosis.

Background and Aims: There is limited evidence about the association of healthy lifestyle and all-cause mortality in individuals with metabolic associated fatty liver disease (MAFLD). We aimed to examine this association and compare it with the association in those without MAFLD. Methods: A prospective cohort study was performed and linked mortality data through 2019 in the National Health Nutrition Examination Survey (NHANES 1999–2010). A healthy lifestyle score was constructed from cigarette smoking, alcohol drinking, healthy eating score, and leisure-time physical activity. Risk stratification was conducted in participants with MAFLD by fibrosis biomarkers and liver enzymes. Survey-weight adjusted Cox regression was used to estimate adjusted hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality associated with healthy lifestyle. Results: There was a protective association between healthy lifestyle and all-cause mortality in participants with MAFLD (HR per 1-unit increase of healthy lifestyle score 0.77 [95% CI 0.69–0.85]), with no difference from the association in participants without MAFLD (HR 0.77 [0.72–0.82]). In participants with MAFLD, the associations tended to be stronger in those with lower risk of advanced fibrosis (HR per 1-unit increase of healthy lifestyle score 0.64 [0.50–0.79] for low NAFLD fibrosis score [NFS] and 0.84 [0.75–0.93] for high NFS, p-value for interaction 0.02), but did not differ by liver enzymes. The results for non-alcoholic fatty liver disease (NAFLD) mirrored those for MAFLD. Conclusions: Healthy lifestyle showed protective associations with all-cause mortality regardless of MAFLD status, and the associations tended to be stronger in those with lower risk of advanced fibrosis. Timely lifestyle modification matters for individuals with MAFLD.

Shimaa Kilany,1 Lmyaa Ata,1 Asmaa Gomaa,1 Aliaa Sabry,1 Ali Nada,1 El-Sayed Tharwa,1 Gamal Badra,1 Ashraf Abogabal,1 Mohamed Elwaraky,2 Enas Moaz,3 Sameera Ezzat,3 Ahmed Elsharawy,4 Imam Waked1 1Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 2Radiology Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 3Epidemiology Department, National Liver Institute, Menoufia University, Menoufia, Egypt; 4Clinical Pathology Department, National Liver Institute, Menoufia University, Menoufia, EgyptCorrespondence: Imam WakedNational Liver Institute, Menoufia University, Shebeen El-Kom, Menoufia, EgyptTel +20-12-2215-7256Fax +20-48-2234586Email iwaked@liver-eg.orgBackground and Aim: Existing data are controversial regarding the incidence of hepatitis C (HCV)–related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4).Methods: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined.Results: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count < 100× 103/mL, and high AFP were independent risk factors of developing HCC.Conclusion: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥ 10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.Keywords: HCC, DAA, HCC incidence, HCC predictors, HCC characteristics

INTRODUCTION: Comparative data on scores that predict outcome in primary biliary cholangitis (PBC) are scarce. We aimed to assess and compare the prognostic value of the Mayo Risk Score (MRS, 1989 and 1994), UK-PBC score, and GLOBE score in a large international cohort of patients with PBC. METHODS: Ursodeoxycholic acid-treated patients from 7 centers participating in the GLOBAL PBC Study Group were included. The discriminatory performance of the scores was assessed with concordance statistics at yearly intervals up to 5 years. Model for End-stage Liver Disease was included for comparison. Prediction accuracy was assessed by comparing predicted survival and actual survival in Kaplan-Meier analyses. RESULTS: A total of 1,100 ursodeoxycholic acid-treated patients with PBC were included, with a mean (SD) age of 53.6 (12.0) years, of whom 1,003 (91%) were female. During a median follow-up of 7.6 (interquartile range 4.1-11.7) years, 42 patients underwent liver transplantation, and 127 patients died. At 1 year, the concordance statistic for Model for End-stage Liver Disease was 0.68 (95% confidence interval [CI] 0.64-0.72), 0.74 (95% CI 0.67-0.80) for the UK-PBC score, 0.76 (95% CI 0.72-0.81) for the MRS (1989 and 1994), and 0.80 (95% CI 0.76-0.84) for the GLOBE score. The GLOBE score showed superior discriminatory performance, but differences were not statistically different. For all scores, discriminatory performance increased in those with bilirubin >0.6 × ULN and advanced fibrosis estimated with Fibrosis-4. The predicted (median) minus observed 5-year transplant-free survival was +0.4% and +2.5% for the MRS (1989) and GLOBE score, respectively. DISCUSSION: All prognostic scores developed for PBC (GLOBE, UK-PBC, and MRS) demonstrated comparable discriminating performance for liver transplantation or death as well as good prediction accuracy.