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Background & Aims: Non-invasive tests (NITs) for liver fibrosis have been recognized for their clinical utility in metabolic dysfunction-associated steatotic liver disease (MASLD). However, their diagnostic efficacy in detecting liver fibrosis is notably reduced in patients with alcohol-related liver disease. Therefore, ascertaining the reliability of NITs in patients with MASLD with moderate alcohol intake (MetALD) is essential., Methods: In this cross-sectional study, we reviewed data from 7,918 health check-up participants who underwent both magnetic resonance elastography (MRE) and ultrasound for the diagnosis of hepatic steatosis. The participants were categorized into MASLD and MetALD groups, and the performance of fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were assessed. Advanced hepatic fibrosis (F3) was defined as MRE ≥3.6 kPa., Results: The prevalence of MetALD was 5.8% in this health check-up cohort, and 1.5% of these patients exhibited advanced hepatic fibrosis. Both MetALD and MASLD displayed similar metabolic profiles and hepatic fibrosis burdens. The diagnostic performance of FIB-4 and NFS for MRE ≥3.6 kPa showed no noticeable differences in the area under the receiver-operating characteristic values between the two groups (0.85 vs. 0.80 in FIB-4). Moreover, the sensitivity (71.4%), specificity (77.3%), and both positive (4.6%) and negative (99.4%) predictive values of NITs for MetALD closely mirrored those observed for MASLD., Conclusion: FIB-4 performed well for the initial screening of advanced hepatic fibrosis in MetALD, demonstrating reasonable sensitivity and negative predictive values., Impact and Implications: In this cross-sectional study, data from 7,918 participants who underwent MRE were analyzed to assess the performance of fibrosis-4 (FIB-4) and non-alcoholic fatty liver disease fibrosis scores in metabolic dysfunction-associated steatotic liver disease (MASLD) and MASLD with moderate alcohol intake (MetALD). We found that FIB-4 had high diagnostic accuracy in the newly identified MetALD group, similar to that in the MASLD population. These results highlight the potential of FIB-4 as a reliable screening tool for MetALD, even when specific subgroups are considered. Therefore, FIB-4 is a valuable screening tool for identifying advanced fibrosis in the MetALD population., (Copyright © 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection., Methods: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed., Results: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log 10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001)., Conclusions: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB., Impact and Implications: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log 10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log 10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk., Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development., Results: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up., Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir., Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance., Competing Interests: Conflict of interest Hwi Young Kim: Nothing to declare; Pietro Lampertico: Speaking bureau/advisor for AbbVie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma, Roche; Joon Yeul Nam: Nothing to declare; Hyung-Chul Lee: Nothing to declare; Seung Up Kim: Receiving grants from Yuhan Pharmaceuticals, and lecture fees from Bristol-Myers Squibb, Gilead Science and Yuhan Pharmaceuticals; Dong Hyun Sinn: Nothing to declare; Yeon Seok Seo: Nothing to declare; Han Ah Lee: Nothing to declare; Soo Young Park: Nothing to declare; Young-Suk Lim: Advisory board member of and receives research funding from Gilead Sciences; Eun Sun Jang: Nothing to declare; Eileen L. Yoon: Nothing to declare; Hyoung Su Kim: Nothing to declare; Sung Eun Kim: Nothing to declare; Sang Bong Ahn: Nothing to declare; Jae-Jun Shim: Nothing to declare; Soung Won Jeong: Nothing to declare; Yong Jin Jung: Nothing to declare; Joo Hyun Sohn: Nothing to declare; Yong Kyun Cho: Nothing to declare; Dae Won Jun: Nothing to declare; George N. Dalekos: Advisor/lecturer for AbbVie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Roche; grant support from Bristol-Myers Squibb, Gilead, Roche; Ramazan Idilman: Nothing to declare; Vana Sypsa: Advisor/lecturer for AbbVie, Gilead, Janssen; research grants from AbbVie, Gilead; Thomas Berg: Advisor/consultant/lecturer for AbbVie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex; Research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche; Maria Buti: Advisor/lecturer for AbbVie, Arbutus, Bristol-Myers Squibb, Gilead, Glaxo Smith-Kleine, Merck, Roche, Spring Bank; Jose Luis Calleja: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck; John Goulis: advisor/lecturer for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche; research grant from Bristol-Myers Squibb; Spilios Manolakopoulos: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche; grants from Bristol-Myers Squibb, Gilead; Harry LA Janssen: Consultant for and grants from AbbVie, Arbutus, Bristol Myers Squibb, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., Viroclinics; Myoung-jin Jang: Nothing to declare; Yun Bin Lee: Research grant from Samjin Pharmaceuticals and Yuhan Pharmaceuticals; Yoon Jun Kim: Research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals and Handok Pharmaceuticals; Jung-eHwan Yoon: Research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals and Daewoong Pharmaceuticals; Jeong-Hoon Lee: Lecture fees from GreenCross Cell, Daewoong Pharmaceuticals and Gilead Korea; George V. Papatheodoridis: Advisor/lecturer for AbbVie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, Spring Bank; research grants AbbVie, Gilead. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Bacterial infections can trigger the development of organ failure(s) and acute-on-chronic liver failure (ACLF). Geographic variations in bacteriology and clinical practice could lead to worldwide differences in ACLF epidemiology, phenotypes and associated outcomes. Herein, we aimed to evaluate regional differences in bacterial infection-related ACLF in patients with cirrhosis admitted to hospital., Methods: This post hoc analysis included 1,175 patients with decompensated cirrhosis (with bacterial infection on admission or nosocomial infection) from 6 geographic regions worldwide. Clinical, laboratory and microbiological data were collected from the diagnosis of infection. Patients were followed-up for organ failure(s) and ACLF development according to the EASL-CLIF criteria from enrolment to discharge/death., Results: A total of 333 patients (28%) had ACLF at diagnosis of infection, while 230 patients developed ACLF after diagnosis of infection, resulting in an overall rate of bacterial infection related-ACLF of 48%, with rates differing amongst different geographic regions (38% in Southern Europe vs. 75% in the Indian subcontinent). Bacterial infection related-ACLF more frequently developed in younger patients (55 ± 13 vs. 58 ± 14 years), males (73% vs. 62%), patients with alcohol-related cirrhosis (59% vs. 45%) and those with a higher baseline MELD score (25 ± 11 vs. 16 ± 5) (all p <0.001). Spontaneous bacterial peritonitis, pneumonia or infections caused by extensively drug resistant (XDR) bacteria were more frequently associated with ACLF development. More patients with ACLF had a positive quick sequential organ failure assessment score and septic shock, resulting in a lower infection resolution rate (all p <0.001)., Conclusions: Bacterial infections, especially with XDR organisms, are associated with the highest risk of ACLF development, accounting for almost half of cases globally. Geographic differences result in variable epidemiology and clinical outcomes., Lay Summary: Bacterial infections can trigger a sudden deterioration in an otherwise stable cirrhotic patient, a condition known as acute-on-chronic liver failure or ACLF. This study has found that the development of ACLF following bacterial infection occurs most commonly in the Indian subcontinent and less so in Southern Europe. The common infections that can trigger ACLF include infection of the abdominal fluid, known as spontaneous bacterial peritonitis, pneumonia and by bacteria that are resistant to multiple antibiotics. Patients who develop ACLF following a bacterial infection have high death rates and are frequently unable to clear the infection., Competing Interests: Conflict of interest Authors declare they have no conflict of interest regarding the content of this manuscript. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020. Published by Elsevier B.V.)

Background & Aims: Recently, new methods, including the concept of viable enhancing tumor such as EASL and mRECIST, have been proposed for substitution of the conventional WHO and RECIST criteria in hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Herein, we evaluated the differences of four methods and compared the association of these methods with the prognosis of HCC patients undergoing TACE., Methods: We retrospectively reviewed 114 consecutive newly diagnosed HCC patients who underwent TACE as initial treatment. We evaluated the intermethod agreement (κ values) between the methods and compared their association with the prognosis of HCC patients., Results: The κ values for EASL vs. WHO, EASL vs. RECIST, mRECIST vs. WHO, and mRECIST vs. RECIST were low, of 0.102, 0.088, 0.112, and 0.122, respectively. However, good correlations were observed for WHO vs. RECIST and EASL vs. mRECIST (κ=0.883, κ=0.759, respectively p<0.001). The median OS was 32.3 months. Hazard ratios (HR) for survival in responders compared with non-responders were 0.21 (95% CI; 0.12-0.37, p<0.001) for EASL and 0.27 (95% CI; 0.15-0.48, p<0.001) for mRECIST. The mean survival of responders was significantly longer than that of non-responders in both EASL (40.8 vs. 16.9 months, p<0.001) and mRECIST (41.1 vs. 20.7 months, p<0.001). In multivariate analysis, EASL response (HR 0.21, 95% CI 0.11-0.40, p<0.001) and mRECIST response (HR; 0.31, 95% CI, 0.17-0.59, p<0.001) were independently associated with survival., Conclusions: The response assessment by EASL and mRECIST could reliably predict the survival of HCC patients undergoing TACE and could be applicable in practice in preference to the conventional WHO and RECIST criteria., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)