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Introduction: Accurate and reliable diagnosis and monitoring of hepatic fibrosis is increasingly important given the variable natural history in chronic liver disease (CLD) and expanding antifibrotic therapeutic options targeting reversibility of early-stage cirrhosis. This highlights the need to develop more refined and effective noninvasive techniques for the dynamic assessment of fibrogenesis and fibrolysis. Areas covered: We conducted a literature review on PubMed, from 1 December 1970, to 1 November 2024, to evaluate and compare available blood-based and imaging-based noninvasive tools for hepatic fibrosis diagnosis and monitoring. Simple scores such as FIB-4 and NAFLD fibrosis score are suitable for excluding significant or advanced fibrosis, while tertiary centers should adopt complex scores and liver stiffness measurement as part of a secondary diagnostic and more comprehensive evaluation. Moreover, the advent of multiomics for high-resolution molecular profiling, and integration of artificial intelligence for noninvasive diagnostics holds promise for revolutionizing fibrosis monitoring and treatment through novel biomarker discovery and predictive omics-based algorithms. Expert opinion: The increased shift toward noninvasive diagnostics for liver fibrosis needs to align with personalized medicine, enabling more effective, tailored management strategies for patients with liver disease in the future. [ABSTRACT FROM AUTHOR]

Background and aimClinical data on the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction and etiology-associated steatohepatitis (MetALD) in a multi-ethnic U.S. population are limited. Additionally, the impact of physical activity (PA) and diet quality (DQ) on the risk of MASLD, MetALD, and compensated advanced chronic liver disease (cACLD) remains unclear. This study aimed to investigate the associations of PA and diet quality with the risks of MASLD, MetALD, and cACLD.Methods and resultsThis cross-sectional study analyzed data from 7,125 participants in the National Health and Nutrition Examination Survey (NHANES) 2017–2020. Diet quality was assessed using the Healthy Eating Index-2015 (HEI-2015). PA was assessed based on the 2020 WHO Physical Activity Guidelines, with participants reporting the intensity, frequency, and duration of their activities over the past 7 days. MASLD and MetALD were diagnosed based on clinical criteria, and cACLD was defined by advanced liver fibrosis. Bivariate and multivariable logistic regression models were used to assess associations between PA, diet quality, and liver disease outcomes. The prevalence of MASLD and MetALD was 35.07 and 21.46%, respectively. HQD was associated with significantly lower risks of MASLD (OR: 0.49, 95% CI: 0.38–0.62) and MetALD (OR: 0.45, 95% CI: 0.36–0.56). High PA levels were linked to reduced risks of MASLD (OR: 0.47, 95% CI: 0.38–0.58) and MetALD (OR: 0.53, 95% CI: 0.39–0.72). The lowest risks for both MASLD and MetALD were observed in highly active participants with an HQD (MASLD OR: 0.41, 95% CI: 0.32–0.53; MetALD OR: 0.54, 95% CI: 0.41–0.71). Significant interactions were observed between PA, HQD, and age, BMI, and SES, which further reduced the risks of MASLD and MetALD. For cACLD, both increased PA and HQD were associated with reduced risk. Compared to non-high-activity participants with a non-HQD, physically active participants with an HQD had the lowest risk of cACLD (OR: 0.44, 95% CI: 0.24–0.82).ConclusionHigh proportions of the US population have MASLD or MetALD. HQD and high PA levels were associated with lower risks of MASLD, MetALD, and cACLD.

Liver stiffness measurement (LSM) is recommended for disease prognostication and monitoring. We evaluated if LSM, using transient elastography, and LSM changes predict decompensation and mortality in patients with alcohol-related liver disease (ALD). We performed an observational cohort study of compensated patients at risk of ALD from Denmark and Austria. We evaluated the risk of decompensation and all-cause mortality, stratified for compensated advanced chronic liver disease (cACLD: baseline LSM ≥10 kPa) and LSM changes after a median of 2 years. In patients with cACLD, we defined LSM changes as (A) LSM increase ≥20% ("cACLD increasers") and (B) follow-up LSM <10 kPa or <20 kPa with LSM decrease ≥20% ("cACLD decreasers"). In patients without cACLD, we defined follow-up LSM ≥10 kPa as an LSM increase ("No cACLD increasers"). The remaining patients were considered LSM stable. We followed 536 patients for 3,008 patient-years–median age 57 years (IQR 49–63), baseline LSM 8.1 kPa (IQR 4.9-21.7)–371 patients (69%) had follow-up LSM after a median of 25 months (IQR 17–38), 41 subsequently decompensated and 55 died. Of 125 with cACLD at baseline, 14% were "cACLD increasers" and 43% "cACLD decreasers", while 13% of patients without cACLD were "No cACLD increasers" (n = 33/246). Baseline LSM, follow-up LSM and LSM changes accurately predicted decompensation (C-index: baseline LSM 0.85; follow-up LSM 0.89; LSM changes 0.85) and mortality (C-index: baseline LSM 0.74; follow-up LSM 0.74; LSM changes 0.70). When compared to "cACLD decreasers", "cACLD increasers" had significantly lower decompensation-free survival and higher risks of decompensation (subdistribution hazard ratio 4.39, p = 0.004) and mortality (hazard ratio 3.22, p = 0.01). LSM by transient elastography predicts decompensation and all-cause mortality in patients with compensated ALD both at diagnosis and when used for monitoring. Patients at risk of alcohol-related liver disease (ALD) are at significant risk of progressive disease and adverse outcomes. Monitoring is essential for optimal disease surveillance and patient guidance, but non-invasive monitoring tools are lacking. In this study we demonstrate that liver stiffness measurement (LSM), using transient elastography, and LSM changes after a median of 2 years, can predict decompensation and all-cause mortality in patients at risk of ALD with and without compensated advanced chronic liver disease. These findings are in line with results from non-alcoholic fatty liver disease, hepatitis C and primary sclerosing cholangitis, and support the clinical utility of LSM, using transient elastography, for disease prognostication and monitoring in chronic liver diseases including ALD, as recommended by the Baveno VII. [Display omitted] • Liver stiffness (LSM) can be used to prognosticate and monitor alcohol-related liver disease. • Elevated baseline LSM (≥10 kPa) was associated with a 19-fold increased risk of decompensation. • LSM changes after a median of 2 years were associated with the risk of decompensation and death. • LSM increasers had lower decompensation-free survival and elevated risk of outcomes. [ABSTRACT FROM AUTHOR]

Background & Aims: The LiverRisk score has been proposed as a blood-based tool to estimate liver stiffness measurement (LSM), thereby stratifying the risk of compensated advanced chronic liver disease (cACLD, LSM ≥10 kPa) and liver-related events in patients without known chronic liver disease (CLD). We aimed to evaluate its diagnostic/prognostic performance in tertiary care. Methods: Patients referred to two hepatology outpatient clinics (cohort I, n = 5,897; cohort II, n = 1,558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed, and diagnostic accuracy for cACLD was compared with that of fibrosis-4 (FIB-4)/aspartate aminotransferase-to-platelet ratio index (APRI). The prediction of hepatic decompensation and utility of proposed cut-offs were evaluated. Results: In cohort I/II, mean age was 48.3/51.8 years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/metabolic dysfunction-associated steatotic liver disease (63.7%), median LSM was 6.9 (IQR 5.1–10.9)/5.8 (IQR 4.5–8.8) kPa, and 1,690 (28.7%)/322 (20.7%) patients had cACLD.Despite a moderate correlation (Pearson’s r = 0.325/0.422), the LiverRisk score systematically underestimated LSM (2.93/1.80 points/kPa lower), and range of agreement was wide, especially at higher values.The diagnostic accuracy of the LiverRisk score for cACLD (area under the receiver operator characteristics curve [AUROC] 0.757/0.790) was comparable to that of FIB-4 (AUROC 0.769/0.813) and APRI (AUROC 0.747/0.765). The proposed cut-off of 10 points yielded an accuracy of 74.2%/81.2%, high specificity (91.9%/93.4%), but low negative predictive value (76.6%/84.5%, Cohen’s κ = 0.260/0.327).In cohort I, 208 (3.5%) patients developed hepatic decompensation (median follow-up 4.7 years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 1–5 years (AUROC 0.778–0.832). However, it was inferior to LSM (AUROC 0.847–0.901, p

The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 - 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals. [ABSTRACT FROM AUTHOR]

The risk of hepatocellular carcinoma (HCC) diminishes in patients with hepatitis C virus (HCV)-related advanced chronic liver disease after virological cure. However, despite viral clearance, HCV-induced epigenetic alterations, immune dysregulations, and hepatic parenchymal injuries remain, contributing to de novo HCC occurrence. While HCC incidence is low (0.45 – 0.5%) in patients with advanced fibrosis (F3), the presence of liver cirrhosis and clinically significant portal hypertension increases the HCC risk. The cost-effectiveness of lifelong HCC surveillance in patients with compensated advanced chronic liver disease (cACLD) has sparked debate, raising questions about the most reliable noninvasive tests and stratification models for predicting HCC in patients with sustained virological response (SVR). Furthermore, identifying cACLD patients who may not require long-term HCC surveillance after SVR remains crucial. Several HCC risk stratification scores have been suggested for patients with cACLD, and emerging evidence supports individualized care based on personalized risk assessments. This review focuses on revising the pretreatment and posttreatment predictors of HCC, as well as the indications for HCC surveillance in cACLD patients treated with direct-acting antivirals.

Background & Aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV. Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma. Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47–3.41) and large (HR 3.86, 95% CI 2.34–6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39–5.05) and large (HR 4.90, 95% CI 2.49–9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16–6.74) or large (HR 5.29, 95% CI 1.96–14.2) OV was also independently associated with incident PVT. Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT. Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality in patients with advanced chronic liver disease (ACLD) caused by chronic hepatitis C who have achieved sustained virologic response (SVR). We developed risk stratification algorithms for de novo HCC development after SVR and validated them in an independent cohort. We evaluated the occurrence of de novo HCC in a derivation cohort of 527 patients with pre-treatment ACLD and SVR to interferon-free therapy, in whom alpha-fetoprotein (AFP) and non-invasive surrogates of portal hypertension including liver stiffness measurement (LSM) were assessed pre-/post-treatment. We validated our results in 1,500 patients with compensated ACLD (cACLD) from other European centers. During a median follow-up (FU) of 41 months, 22/475 patients with cACLD (4.6%, 1.45/100 patient-years) vs. 12/52 decompensated patients (23.1%, 7.00/100 patient-years, p < 0.001) developed de novo HCC. Since decompensated patients were at substantial HCC risk, we focused on cACLD for all further analyses. In cACLD, post-treatment-values showed a higher discriminative ability for patients with/without de novo HCC development during FU than pre-treatment values or absolute/relative changes. Models based on post-treatment AFP, alcohol consumption (optional), age, LSM, and albumin, accurately predicted de novo HCC development (bootstrapped Harrel's C with/without considering alcohol: 0.893/0.836). Importantly, these parameters also provided independent prognostic information in competing risk analysis and accurately stratified patients into low- (~2/3 of patients) and high-risk (~1/3 of patients) groups in the derivation (algorithm with alcohol consumption; 4-year HCC-risk: 0% vs. 16.5%) and validation (3.3% vs. 17.5%) cohorts. An alternative approach based on alcohol consumption (optional), age, LSM, and albumin (i.e. , without AFP) also showed a robust performance. Simple algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified patients with cACLD based on their risk of de novo HCC after SVR. Approximately two-thirds were identified as having an HCC risk <1%/year in both the derivation and validation cohort, thereby clearly falling below the cost-effectiveness threshold for HCC surveillance. Simple algorithms based on age, alcohol consumption, results of blood tests (albumin and α-fetoprotein), as well as liver stiffness measurement after the end of hepatitis C treatment identify a large proportion (approximately two-thirds) of patients with advanced but still asymptomatic liver disease who are at very low risk (<1%/year) of liver cancer development, and thus, might not need to undergo 6-monthly liver ultrasound. [Display omitted] • We studied de novo HCC development in patients with cACLD after SVR in a derivation cohort (n = 475) and validation cohort (n = 1,500). • Algorithms based on post-treatment age/albumin/LSM, and optionally, AFP and alcohol consumption, accurately stratified de novo HCC risk. • Approximately two-thirds of patients were identified as having an HCC risk <1%/year. • In these patients, HCC-surveillance might not be cost-effective. [ABSTRACT FROM AUTHOR]

Introduction: Nonalcoholic fatty liver disease (NAFLD) patients can progress to cirrhosis. In these, there is a compensated stage in which esophageal varices can exist. However, no more than 20% of these patients have varices needing treatment (VNT). Objective: Evaluate the accuracy of non-invasive models to predict esophageal varices, as well as their performance to avoid esophagogastroduodenoscopy (EGD) with a risk of missing VNT of less than 5%, in Brazilian patients with compensated advanced chronic liver disease (cACLD) secondary to NAFLD. Methods: Twenty-one patients with biopsy-proven cACLD secondary to NAFLD were submitted to liver stiffness measurement (LSM) by transient elastography (TE), and data were collected to measure platelet count/spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS), varices risk score (VRS), Baveno VI, Expanded Baveno VI and NAFLD cirrhosis criteria. Results: The mean age was 61 (±6.6) years, and 81% were female; 14% presented VNT. For detection of VNT, LSPS and VRS performed excellently, with an area under receiver operating characteristic (AUROC) of 0.961 for both. LSM presented an AUROC of 0.889 and a cutoff point of 21.8 kPa. LSPS and VRS enabled sparing 75–80% of EGDs for VNT, with no risk of missing varices. Expanded Baveno VI enabled sparing 71% of EGDs, with 4.8% risk of missing VNT. Conclusion: LSPS and VRS performed excellently in both predicting VNT and sparing EGD, and Expanded Baveno VI showed good performance in sparing EGDs, with acceptable risk of missing VNT. An LSM cutoff point was established and had good performance.

Introduction: Nonalcoholic fatty liver disease (NAFLD) patients can progress to cirrhosis. In these, there is a compensated stage in which esophageal varices can exist. However, no more than 20% of these patients have varices needing treatment (VNT). Objective: Evaluate the accuracy of non-invasive models to predict esophageal varices, as well as their performance to avoid esophagogastroduodenoscopy (EGD) with a risk of missing VNT of less than 5%, in Brazilian patients with compensated advanced chronic liver disease (cACLD) secondary to NAFLD. Methods: Twenty-one patients with biopsy-proven cACLD secondary to NAFLD were submitted to liver stiffness measurement (LSM) by transient elastography (TE), and data were collected to measure platelet count/spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS), varices risk score (VRS), Baveno VI, Expanded Baveno VI and NAFLD cirrhosis criteria. Results: The mean age was 61 (±6.6) years, and 81% were female; 14% presented VNT. For detection of VNT, LSPS and VRS performed excellently, with an area under receiver operating characteristic (AUROC) of 0.961 for both. LSM presented an AUROC of 0.889 and a cutoff point of 21.8 kPa. LSPS and VRS enabled sparing 75-80% of EGDs for VNT, with no risk of missing varices. Expanded Baveno VI enabled sparing 71% of EGDs, with 4.8% risk of missing VNT. Conclusion: LSPS and VRS performed excellently in both predicting VNT and sparing EGD, and Expanded Baveno VI showed good performance in sparing EGDs, with acceptable risk of missing VNT. An LSM cutoff point was established and had good performance. [ABSTRACT FROM AUTHOR]

Background: Baveno VI criteria for screening varices needing treatment (VNT) have not yet been validated in an exclusive pediatric and adolescent set of the population, in whom baseline parameters differ in relation to adults. Therefore, our primary objective was to validate Baveno VI and its expanded form in children below 18 years of age. The secondary aim was to elicit whether any revision of the above criteria with a target of not missing more than 5% VNT could be more accurate for this age group. Materials and Methods: The work was carried out in two medical institutes, over a span of 3 years. Consecutively enrolled patients below 18 years of age, with compensated cirrhosis confirmed by liver biopsy, were evaluated for related blood parameters, transient elastography (TE) and esophagogastroduodenoscopy. Results: Out of the 33 recruited patients, five (15.15%) met the criteria for VNT. The sensitivity, specificity, PPV and NPV of Baveno VI and Expanded Baveno VI were observed as 60%, 92.3%, 60% and 92.3%, and 20%, 100%, 100% and 88%, respectively. We found that the Revised Baveno VI criteria with TE < 19 kPa and platelet count of > 175× 109 cells/L, with sensitivity 100%, specificity 79%, PPV 45%, NPV 100% and accuracy of 82%, are more appropriate for this age group. Conclusion: We propose that further multicentrer studies with a larger sample size should be conducted before incorporating Revised Baveno VI criteria for high-risk varices in patients below 18 years in future guidelines. [ABSTRACT FROM AUTHOR]

The aim of this study was to predict the presence of esophageal varices (EVs) by noninvasive tools combined with 2-dimensional shear wave elastography (2D-SWE), and to compare the diagnostic capabilities of 2D-SWE with those of transient elastography (TE). Between January 2015 and December 2017, 289 patients with compensated advanced chronic liver disease (cACLD) who underwent consecutive 2D-SWE and EGD were enrolled. Capabilities for predicting the presence of EVs of 2D-SWE and models combining 2D-SWE with other noninvasive tools (modified LS-spleen-diameter-to-platelet-ratio score [mLSPS], platelet-spleen ratio score) were compared. A subgroup analysis was performed on 177 patients who also underwent simultaneous TE. The area under receiver operating characteristics (AUROCs) for detecting EVs for 2D-SWE alone vs. mLSPS, which included 2D-SWE, were 0.757 (95% confidence interval [CI], 0.701–0.810) and 0.813 (95% CI, 0.763–.857), respectively. The AUROCs for predicting varices needing treatment (VNT) for 2D-SWE and mLSPS were 0.712 (95% CI, 0.621–0.738) and 0.834 (95% CI, 0.785–0.875), respectively. For the 195 patients who underwent simultaneous TE and 2D-SWE, no differences in diagnostic performance were observed. The diagnostic performance of 2D-SWE is similar to that of TE for predicting the presence of EVs. The mLSPS, which includes 2D-SWE, seemed to be useful for predicting EVs. [ABSTRACT FROM AUTHOR]

Patients with advanced fibrosis related to nonalcoholic fatty liver disease (NAFLD) are at risk of developing hepatic and extrahepatic complications. We investigated whether, in a large cohort of patients with NAFLD and compensated advanced chronic liver disease, baseline liver stiffness measurements (LSMs) and their changes can be used to identify patients at risk for liver-related and extrahepatic events. We performed a retrospective analysis of consecutive patients with NAFLD (n = 1039) with a histologic diagnosis of F3–F4 fibrosis and/or LSMs>10 kPa, followed for at least 6 months, from medical centers in 6 countries. LSMs were made by FibroScan using the M or XL probe and recorded at baseline and within 1 year from the last follow-up examination. Differences between follow up and baseline LSMs were categorized as: improvement (reduction of more than 20%), stable (reduction of 20% to an increase of 20%), impairment (an increase of 20% or more). We recorded hepatic events (such as liver decompensation, ascites, encephalopathy, variceal bleeding, jaundice, or hepatocellular carcinoma [HCC]) and overall and liver-related mortality during a median follow-up time of 35 months (interquartile range, 19–63 months). Based on Cox regression analysis, baseline LSM was independently associated with occurrence of hepatic decompensation (hazard ratio [HR], 1.03; 95% CI, 1.02–1.04; P <.001), HCC (HR, 1.03; 95% CI, 1.00–1.04; P =.003), and liver-related death (HR, 1.02; 95% CI, 1.02–1.03; P =.005). In 533 patients with available LSMs during the follow-up period, change in LSM was independently associated with hepatic decompensation (HR, 1.56; 95% CI, 1.05–2.51; P =.04), HCC (HR, 1.72; 95% CI, 1.01–3.02; P =.04), overall mortality (HR, 1.73; 95% CI, 1.11–2.69; P =.01), and liver-related mortality (HR, 1.96; 95% CI, 1.10–3.38; P =.02). In patients with NAFLD and compensated advanced chronic liver disease, baseline LSM and change in LSM are associated with risk of liver-related events and mortality. [ABSTRACT FROM AUTHOR]