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Background and Aims: Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis. Methods: Primary care patients at increased risk for MASLD with advanced fibrosis (n = 91,914) were identified using previously established criteria. Patients with known alternative/concomitant etiology of liver disease or cirrhosis were excluded. The study cohort included patients with calculated FIB-4 score in 2020 (n = 52,006), and stratified into low, indeterminate, and high likelihood of advanced fibrosis. Among those at indeterminate/high risk, rates of subsequent testing were measured. Results: Risk stratification with FIB-4 characterized 77% (n = 40,026) as low risk, 17% (n = 8847) as indeterminate, and 6% (n = 3133) as high risk. Among indeterminate/high-risk patients (n = 11,980), 78.7% (n = 9433) had aminotransferases within normal limits, 0.95% (n = 114) had elastography, and 8.2% (n = 984) were referred for subspecialty evaluation. Conclusion: In this cohort of primary care patients at risk for MASLD with fibrosis, the FIB-4 score identified a substantial proportion of indeterminate/high-risk patients, the majority of which had normal aminotransferase levels. Low rates of subsequent testing were observed. These data suggest that a majority of patients at increased risk for liver-related outcomes remain unrecognized and highlight opportunities to facilitate their identification. [ABSTRACT FROM AUTHOR]

Background: As the global epidemic of obesity fuels metabolic conditions, the burden of nonalcoholic fatty liver disease (NAFLD) will become enormous. Abundant studies revealed the association between high body mass index (BMI) and NAFLD but overlooked the BMI patterns across life stages. We aimed to explore how BMI trajectories over age relate to NAFLD. Methods: Selecting 3212 participants in NHANES 2017–2020, we tracked BMI records at different ages. Using a latent class trajectory model (LCTM), we identified BMI trajectories over age. Multinomial logistic regression assessed their association with NAFLD and advanced fibrosis. Structural equation modeling (SEM) revealed mediation effects. Results: We identified 3 BMI trajectories: Steady Progression, Increase to Decrease, and Rapid Ascending. There was no significant difference in NAFLD/advanced fibrosis risk between the increase-to-decrease group and the steady progression group. The Rapid Ascending trajectory significantly correlated with NAFLD (OR = 2.21, 95% CI 1.29–3.77) and advanced fibrosis (OR = 3.04, 95% CI 1.13–8.22). This association was influenced by a chain-mediated process of phenotypic age and C-reactive protein (mediated effect to NAFLD = 0.010, p < 0.01; mediated effect to advanced fibrosis = 0.003, p < 0.05). This mediation on NAFLD was independent of insulin resistance (IR). The association between rapid ascending trajectory and advanced fibrosis was more pronounced among the male subgroup (p for interaction = 0.008). Conclusion: The rapid ascending trajectory of BMI correlates with an increased susceptibility to NAFLD and advanced fibrosis independent of BMI, mediated by aging and inflammation. Our results suggest that long-term maintenance of BMI is pivotal in NAFLD prevention. Aging-inflammation may represent a distinct mechanism of sustained obesity to NAFLD, independent of IR. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B (HBV) and Delta (HDV) virus infections pose critical public health challenges, particularly in Romania, where HDV co-infection is underdiagnosed. Methods: This study investigates the epidemiology, risk factors, and clinical outcomes of HBV/HDV co-infection in vulnerable populations, leveraging data from the LIVE(RO2) program. Conducted between July 2021 and November 2023, the program screened 320,000 individuals across 24 counties, targeting socially disadvantaged groups such as rural residents, the Roma community, and those lacking health insurance. Results: Among 6813 hepatitis B surface antigen (HBsAg)-positive individuals, HDV antibody prevalence was 4.87%, with active replication confirmed in 75.6% of HDV-positive cases. Regional disparities emerged, with higher HDV prevalence and replication rates in the Eastern region compared to the South. HDV-positive individuals were more likely to be younger, male, and from rural or socioeconomically disadvantaged backgrounds. Clinically, HDV co-infection correlated with increased liver stiffness, advanced fibrosis stages, and lower steatosis levels compared to HBV mono-infection. Psychiatric comorbidities were more prevalent among HDV-positive patients, highlighting the need for integrated care. Conclusions: This study underscores the urgent need for targeted public health interventions, including enhanced screening, education, and access to novel antiviral therapies like bulevirtide to address the significant burden of HBV/HDV co-infection in Romania. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and Aims Methods Results Conclusions Metabolic dysfunction‐associated steatotic liver disease (MASLD) is responsible for a significant global health burden. Despite this burden, the prevalence and mortality of MASLD‐related cirrhosis remain inadequately defined, hindering effective public health strategies. This study aimed to estimate the global prevalence and mortality associated with MASLD‐related cirrhosis.A systematic search of PubMed, Ovid MEDLINE, EMBASE, Web of Science and SCOPUS was conducted using keywords related to MASLD and cirrhosis from inception of each database used through June 2024. COVIDENCE was used for abstract and manuscript review. MASLD populations were categorised into ‘general practice setting’ and ‘high risk setting’, which indicated studies from inpatient setting or those referred for liver biopsy for an indication (elevated liver enzymes). Our data extraction and quality assessment followed PRISMA guidelines. A random‐effects model was utilised for meta‐analysis.From 7924 identified articles, 35 studies comprising 513,742 patients with MASLD met the inclusion criteria. The pooled global prevalence of cirrhosis among MASLD patients was 3.26% (95% CI: 2.47%–4.31%) in general practice settings (4 studies) and 14.51% (95% CI: 11.22%–18.57%) among those in inpatient settings or referred for liver biopsy (31 studies). Regionally, higher prevalence rates in high‐risk settings were observed in North America and Australia (18.38%; 95% CI: 9.06%–33.75%), followed by Europe (10.16%; 95% CI: 5.71%–17.44%) and Asia (9.12%; 95% CI: 6.11%–13.40%) (p = 0.007). Notably, ICD‐based diagnoses indicated a significantly higher prevalence of cirrhosis (27.43%) compared to those diagnosed by liver biopsy (13.24%; p < 0.001). The pooled all‐cause mortality rate for MASLD‐cirrhosis patients was estimated at 7.91 per 100 person‐years (95% CI: 4.44–13.71) (9 studies).This meta‐analysis underscores the substantial prevalence of cirrhosis among MASLD patients and highlights significant geographic and demographic variability, calling for improved screening and management strategies. [ABSTRACT FROM AUTHOR]

Background and Aim: The prevalence of metabolic dysfunction‐associated steatotic liver disease (MASLD) is increasing worldwide, coinciding with aging population. However, limited studies have evaluated its incidence and progression to advanced fibrosis in the elderly population. Therefore, our study aimed to investigate the incidence of MASLD and advanced fibrosis in this age group. Methods: We included 878 686 individuals aged ≥60 years from the Korea National Health Insurance Service‐Senior cohort. After excluding participants with preexisting MASLD, 329 388 individuals were finally analyzed. Participants were categorized into four groups based on the presence of overweight/obesity and additional risk factors (aRF) included in the cardiometabolic diagnostic criteria of MASLD. Results: The overall incidence of MASLD was 1.94 per 100 person‐years, and the incidence of advanced fibrosis in MASLD patients was 1.78 per 100 person‐years. MASLD development was significantly higher in overweight/obese patients (2.65 per 100 person‐years) compared to lean patients (1.09 per 100 person‐years), and this trend persisted after stratification by the presence of aRF. Similarly, the incidence of advanced fibrosis among MASLD patients was higher in overweight/obese individuals (2.06 per 100 person‐years) compared to lean counterparts (0.87 per 100 person‐years), irrespective of aRF. Conclusions: The lower incidence of MASLD in the elderly population compared to the general population underscores the importance of identifying age‐specific risk factors. Overweight/obesity emerged as a robust predictor of MASLD development and advanced fibrosis. Additionally, the presence of additional cardiometabolic risk factors further increased the risk of incident MASLD and advanced fibrosis among the elderly. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is a significant risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). Traditionally, the primary prevention strategy for HCV-associated HCC has focused on removing infection through antiviral regimes. Currently, highly effective direct-acting antivirals (DAAs) offer extraordinary success across all patient categories, including cirrhotics. Despite these advancements, recent studies have reported that even after sustained virologic response (SVR), individuals with advanced liver disease/cirrhosis at the time of DAA treatment may still face risks of HCC occurrence or recurrence. Based on this premise, this review tries to shed light on the multiple mechanisms that establish a tumorigenic environment, first, during chronic HCV infection and then, after eventual viral eradication by DAAs. Furthermore, it reviews evidence reported by recent observational studies stating that the use of DAAs is not associated with an increased risk of HCC development but rather, with a significantly lower chance of liver cancer compared with DAA-untreated patients. In addition, it seeks to provide some practical guidance for clinicians, helping them to manage HCC surveillance of patients who have achieved SVR with DAAs. [ABSTRACT FROM AUTHOR]

Background and Aim: Patients with type 2 diabetes mellitus (T2DM) face a heightened susceptibility to advanced fibrosis, a condition linked to adverse clinical outcomes. However, reported data on liver fibrosis severity among individuals with T2DM vary significantly across studies with diverse characteristics. This meta‐analysis aimed to estimate the global prevalence of advanced fibrosis among T2DM patients. Methods: A comprehensive systematic search of the EMBASE and MEDLINE databases from inception to November 2022 was conducted to identify studies assessing advanced fibrosis in individuals with T2DM. Random‐effects models were utilized to calculate point estimates of prevalence, accompanied by 95% confidence interval (CI). Meta‐regression with subgroup analysis was employed to address heterogeneity. Results: We identified 113 eligible studies involving 244,858 individuals from 29 countries. Globally, the prevalence of advanced fibrosis among T2DM patients was 19.5% (95% CI 16.8–22.4%). Regionally, the prevalence rates were as follows: 60.5% in West Asia (95% CI 50.3–70.4%), 24.4% in South Asia (95% CI 16.2–33.7%), 20.1% in East Asia (95% CI 14.7–26.1%), 20.0% in Europe (95% CI 15.8–24.6%), 15.8% in North America (95% CI 11.0–21.3%), and 11.3% in South America (95% CI 6.2–17.5%). The prevalence of advanced fibrosis varied notably based on the study setting and diagnostic methodology employed. Meta‐regression models highlighted that 45.13% of the observed heterogeneity could be attributed to combined diagnostic modality and study setting. Conclusions: Globally, approximately one fifth of the T2DM population presents advanced fibrosis, with prevalence differing across geographical regions. Our findings underscore the need for effective strategies to alleviate its global burden. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction associated steatotic liver disease (MASLD) has a strong genetic component. The aim of this study was to examine noninvasively the prevalence of MASLD and of advanced fibrosis in relatives of patients with advanced MASLD and the risk factors for liver involvement, with a focus on the contribution of common genetic risk variants. We prospectively enrolled 98 consecutive probands with advanced fibrosis and/or hepatocellular carcinoma caused by MASLD and 160 nontwin first-degree relatives noninvasively screened for MASLD and advanced fibrosis at 4 Italian centers. We evaluated common genetic determinants and polygenic risk scores of liver disease. Among relatives, prevalence of MASLD was 56.8% overall, whereas advanced fibrosis was observed in 14.4%. At multivariable analysis in relatives, MASLD was associated with body mass index (odds ratio [OR], 1.31 [1.18–1.46]) and tended to be associated with diabetes (OR, 5.21 [0.97–28.10]), alcohol intake (OR, 1.32 [0.98–1.78]), and with female sex (OR, 0.54 [0.23–1.15]), whereas advanced fibrosis was associated with diabetes (OR, 3.13 [1.16–8.45]) and nearly with body mass index (OR, 1.09 [1.00–1.19]). Despite that the PNPLA3 risk variant was enriched in probands (P =.003) and overtransmitted to relatives with MASLD (P =.045), evaluation of genetic risk variants and polygenic risk scores was not useful to guide noninvasive screening of advanced fibrosis in relatives. We confirmed that about 1 in 7 relatives of patients with advanced MASLD has advanced fibrosis, supporting clinical recommendations to perform family screening in this setting. Genetic risk variants contributed to liver disease within families but did not meaningfully improve fibrosis risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]

BackgroundThis study aims to evaluate the association between hypertension and the risk of fibrosis in metabolic dysfunction–associated steatotic liver disease (MASLD) patients, as well as to investigate the impact of hypertension on the progression of liver fibrosis within this population.MethodsWe utilized data from the NHANES 2017 to March 2020. Multivariate logistic regression models were employed to control for sociodemographic and metabolic factors to determine the associations between hypertension, MASLD, and fibrosis.ResultsOf the total cohort (N = 5,967) 57.92% had hypertension, 38.8% had MASLD, 25.88% had both MASLD and hypertension. Patients with MASLD were more likely to have hypertension (64.24% vs. 44.80%). There was a significant association between stage I (OR1.70, 95% CI: 1.15–2.53) and stage II hypertension (OR1.98, 95% CI: 1.38–2.85) and an increased risk of SF. After adjusting for multiple confounding factors, stage I (OR1.59, 95% CI: 1.09–2.24) and stage II hypertension (OR1.48, 95% CI: 1.06–2.06) remained significantly associated with the risk of SF. Patients with both MASLD and hypertension had higher rates of SF at 14.83% and AF at 7.47%. After adjusting for sociodemographic factors, those patients still had an 8.02-fold increased risk of SF (OR8.02, 95% CI: 4.47–14.39) and a 15.13-fold increased risk of AF (OR15.13, 95% CI: 7.09–32.3). Further adjustment for metabolic factors, those patients still had a significantly higher risk of SF (OR3.07, 95% CI: 1.83–5.14) and AF (OR4.01, 95% CI: 1.48–10.89).ConclusionMASLD and hypertension are at risk for fibrosis, and the coexistence of the two has a more significant impact on the risk of fibrosis.

BackgroundNonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with advanced fibrosis increasing mortality risks. Despite the abundance of dietary guidelines for managing NAFLD, the precise impact of diet quality on mortality among individuals with advanced fibrosis remains elusive. This study aims to explore the influence of five dietary quality indexes on mortality among NAFLD patients and advanced fibrosis patients.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 to assess dietary quality based on the Alternate Mediterranean Diet (aMED), Healthy Eating Index-2020 (HEI-2020), Dietary Approach to Stop Hypertension (DASH), Alternate Healthy Eating Index (AHEI), and Dietary Inflammatory Index (DII). Weighted Cox proportional hazard regression models along with restricted cubic splines and subgroup analyses were employed in this study.ResultsThe analysis encompassed 3,634 NAFLD patients. After a median follow-up of 89 months, it was found that higher scores on the aMED (HR 0.814, 95% CI 0.681–0.972), HEI-2020 (HR 0.984, 95% CI 0.972–0.997), DASH (HR 0.930, 95% CI 0.883–0.979), and AHEI (HR 0.980, 95% CI 0.966–0.995) were associated with lower mortality risks, while DII scores (HR 1.280, 95% CI 1.098–1.493) indicated an increased risk of mortality. Additionally, a nonlinear relationship was identified solely between AHEI scores and all-cause mortality in NAFLD patients. Notably, among patients with advanced fibrosis, HEI-2020 as a categorical variable (T3: HR 0.519, 95% CI 0.280–0.964), DASH as a continuous variable (continuous: HR 0.921, 95% CI 0.849–0.999), AHEI (continuous: HR 0.971, 95% CI 0.945–0.997; T2: HR 0.545, 95% CI 0.310–0.960; T3: HR 0.444, 95% CI 0.245–0.804), and DII (continuous: HR 1.311, 95% CI 1.121–1.534; T3: HR 2.772, 95% CI 1.477–5.202) exhibited significant associations with all-cause mortality. Subgroup analyses revealed an interaction between AHEI scores and sex among NAFLD patients, where higher AHEI scores correlated with lower all-cause mortality in females, but no such association was observed in males. For other dietary quality, subgroup analyses indicated that their relationships with mortality were robust.ConclusionOur study suggests that a high-quality diet could potentially mitigate mortality risk in both NAFLD and advanced fibrosis patients.

Abstract People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p

Abstract Background Studies attempted to estimate MASLD-related advanced fibrosis (AF) and cirrhosis (MC) prevalence utilized tests with low positive predictive value (PPV) which overestimates prevalence. AGILE3 + and 4 scores were developed to increase the PPV of both; respectively. In this study, we used these scores to assess the prevalence of AF and MC. Methods Participants aged ≥ 18 years with VCTE exam in the NHANES 2017–2018 cycle were included. We excluded pregnant women, patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L. MASLD was defined with CAP score > 248 dB/m. MASLD subjects with AGILE 3 + score of ≥ 0.68 and AGILE 4 score of ≥ 0.57 were considered to have advanced fibrosis and cirrhosis; respectively. AGILE 3 + of 0.45–0.67 and AGILE 4 of 0.25–0.57 were grey zone, whereas AGILE 3 +

People with type 2 diabetes mellitus (T2DM) show a high prevalence of steatotic liver disease (SLD), and especially metabolic dysfunction-associated steatotic liver disease (MASLD), with liver fibrosis. Their health-related quality of life (HRQL) is affected by multiple in part overlapping factors and aggravated by metabolic and liver-related comorbidities, including liver fibrosis stage. The aim of this study was to investigate the effect size of advanced fibrosis (AF) on the HRQL in people with T2DM. A total of 149 individuals with T2DM treated at a primary care provider within the German disease management program (DMP) were included in the final analysis. Vibration-controlled transient elastography (VCTE) was used to non-invasively detect steatosis and AF. The EQ-5D-3L questionnaire was used to assess the HRQL. Uni- and multivariable linear regression models were used to identify independent predictors of impaired HRQL. The majority was male (63.1%), and the median age was 67 years (IQR 59; 71). In the entire cohort, the prevalence of MASLD and AF was 70.7% and 19.5%, respectively. People with T2DM and AF had an overall lower HRQL in comparison to those without AF (p < 0.001). Obesity (β: − 0.247; 95% CI − 0.419, − 0.077) and AF (β: − 0.222; 95% CI − 0.383, − 0.051) remained independent predictors of a poor HRQL. In turn, T2DM-related comorbidities were not predictive of an impaired HRQL. Obesity and AF negatively affect the HRQL in patients with SLD and T2DM in primary care. Awareness of liver health and specific interventions may improve patient-reported and liver-related outcomes in people with T2DM. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is less frequent in non-Hispanic persons (NHB), but there are knowledge gaps in our understanding of disease severity and outcomes of NAFLD in NHB. We compared liver histology and clinical outcomes of NAFLD in non-Hispanic Black persons (NHB) and non-Hispanic White persons (NHW). METHODS: We compared liver histology and outcomes of 109 NHB and 1,910 NHW adults with biopsy-proven NAFLD participating in the Nonalcoholic Steatohepatitis Clinical Research Network observational studies. The relationship between self-reported NHB race/ethnicity and advanced fibrosis was assessed through multivariable logistic regression after controlling for clinical covariates and PNPLA3 genotype. RESULTS: NHB and NHW with NAFLD had similar NAFLD activity scores (NAS, 4.4 vs 4.3, P = 0.87) and proportions with definite metabolic dysfunction-associated steatohepatitis (59% vs 58%, P = 1.0), but NHB had significantly lower rates of advanced fibrosis (22% vs 34%, P = 0.01) or cirrhosis (4.6% vs 12.1%, P = 0.010). Compared with NHW, NHB had significantly lower frequency of advanced fibrosis (Odds Ratio: 0.48, 95% Confidence Interval: 27-0.86, P = 0.01). In a comparison between 24 NHB and 655 NHW with advanced fibrosis, the NAS (5.6 vs 4.9, P = 0.01) and lobular inflammation grade (2.2 vs 1.7, P < 0.002) were significantly higher among NHB with advanced fibrosis. One NHB and 23 NHW died during follow-up (0.30 vs 0.28 per 100 person-year follow-up). Seven and zero liver-related deaths occurred in NHW and NHB with NAFLD, respectively. DISCUSSION: The risk of advanced fibrosis in NHB with NAFLD is significantly lower, after controlling for clinical risk factors and PNPLA3 genotype. Although their risk of advanced fibrosis was low, NHB with NAFLD and advanced fibrosis had higher NAS and lobular inflammation, indicating a difference in their relationship between necroinflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally, with an estimated prevalence exceeding 25%. Variants in the PNPLA3 and HSD17B13 genes have been a focus of investigations surrounding the etiology and progression of NAFLD and are believed to contribute to a greater burden of disease experienced by Hispanic Americans. However, little is known about socioeconomic factors influencing NAFLD progression or its increased prevalence among Hispanics. Materials and Methods: We cross‐sectionally analyzed 264 patients to assess the role of genetic and socioeconomic variables in the development of advanced liver fibrosis in individuals at risk for NAFLD. Results: Adjusting for age, sex, body mass index, and PNPLA3 genotype, lacking a college degree was associated with 3.3 times higher odds of advanced fibrosis (95% confidence interval [CI]: 1.21–8.76, p = 0.019), an effect comparable to that of possessing the major PNPLA3 risk variant. Notably, the effect of PNPLA3 genotype on advanced fibrosis was attenuated to nonsignificance following adjustment for education and other socioeconomic markers. The effect of the protective HSD17B13 variant, moreover, diminished after adjustment for education (odds ratio [OR]: 0.39 [95% CI: 0.13–1.16, p = 0.092]), while lower education continued to predict advanced fibrosis following multivariable adjustment with an OR of 8.0 (95% CI: 1.91–33.86, p = 0.005). Discussion: Adjusting for education attenuated the effects of genotype and Hispanic ethnicity on liver fibrosis, suggesting that social factors—rather than genes or ethnicity—may be driving disease severity within some populations. Findings reveal the importance of including socioenvironmental controls when considering the role of genetics or ethnicity in complex disease. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Steatotic liver disease is common in people with HIV (PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with AF assessed by liver stiffness measurement (LSM). METHODS: We prospectively collected data on adults participating in 2 National Institute of Health-sponsored HIV NAFLD networks. All had HIV on antiretroviral therapy (ART) ≥6 months with HIV RNA <200 copies/mL. Those with viral hepatitis, other liver disease, excessive alcohol use, or hepatic decompensation were excluded. Vibration-controlled transient elastrography for LSM was performed, and AF defined as ≥11 kPa was compared with FIB-4 and NFS at predefined thresholds (<1.3 and >2.67 for FIB-4 and <-1.455 and >0.675 for NFS). RESULTS: A total of 1,065 participants were analyzed: mean age 51.6 years, 74% male, 28% White, 46% Black, 22% Hispanic, with 34% overweight (body mass index 25-29 kg/m²) and 43% obese (body mass index ≥30 kg/m²). Features of the metabolic syndrome were common: hyperlipidemia 35%, type 2 diabetes 17%, and hypertension 48%. The median CD4+ T-cell count was 666 cells/mm³, 74% had undetectable HIV RNA, and duration of HIV-1 was 17 years with most taking a nucleoside reverse transcriptase inhibitor (92%) and an integrase inhibitor (83%). The mean LSM was 6.3 kPa, and 6.3% had AF. The area under the receiver characteristic curve for FIB-4 and NFS to identify AF were 0.70 and 0.75, respectively. While both had high negative predictive values (97%-98%), the sensitivity at low thresholds and specificity at high thresholds were 64% and 97% for FIB-4 and 80% and 96% for NFS, respectively. Neither FIB-4 nor NFS at either threshold had good positive predictive value to detect AF. DISCUSSION: FIB-4 and NFS have excellent specificity and negative predictive value for detecting AF, and thus can be used as screening tools in PWH to exclude those with AF who do not need further testing (LSM) or referral to hepatologist. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (55%) and are at increased risk for developing non-alcoholic steatohepatitis, a severe form of NAFLD. Early detection of advanced fibrosis in patients with T2D and NAFLD is crucial and can prevent progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. However, screening for liver disease and risk-stratification pathways are not established in patients with T2D. We evaluated the efficacy of using the automated fibrosis-4 (FIB-4) index in routine clinical settings to identify patients requiring further specialist evaluation. Materials and Methods: In this prospective cohort study, individuals diagnosed with T2D were recruited from diabetes clinics at a tertiary university hospital. Demographic, clinical, and laboratory data were comprehensively collected. The FIB-4 index was automatically calculated and integrated into the hospital's electronic medical records (EMRs), which were then stratified by age. Patients with advanced fibrosis (FIB-4 index ≥ 1.3) were referred to a specialist. Student's t-test or the Mann–Whitney U test was used to analyze variables associated with advanced fibrosis. Logistic regression was used to identify predictors of advanced fibrosis. Results: Among the 318 patients with T2D, 9.7% had advanced fibrosis. The majority were females (54.7%) and Saudi nationals (89.6%). Several factors, including age, platelet count, total bilirubin, serum albumin, total cholesterol, low-density lipoprotein, transaminases, and gamma-glutamyl transferase (GGT), showed significant associations with advanced fibrosis (all p < 0.05). Older age, elevated total bilirubin and GGT levels, and prolonged international normalized ratio emerged as independent predictors of advanced fibrosis. Conclusions: Integrating the FIB-4 index into the EMR during the routine care of patients with T2D proved to be a valuable tool in effectively identifying individuals at risk of advanced fibrosis. Our findings emphasize the need for further research to refine screening strategies in this high-risk population. [ABSTRACT FROM AUTHOR]

Background: Studies attempted to estimate MASLD-related advanced fibrosis (AF) and cirrhosis (MC) prevalence utilized tests with low positive predictive value (PPV) which overestimates prevalence. AGILE3 + and 4 scores were developed to increase the PPV of both; respectively. In this study, we used these scores to assess the prevalence of AF and MC. Methods: Participants aged ≥ 18 years with VCTE exam in the NHANES 2017–2018 cycle were included. We excluded pregnant women, patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L. MASLD was defined with CAP score > 248 dB/m. MASLD subjects with AGILE 3 + score of ≥ 0.68 and AGILE 4 score of ≥ 0.57 were considered to have advanced fibrosis and cirrhosis; respectively. AGILE 3 + of 0.45–0.67 and AGILE 4 of 0.25–0.57 were grey zone, whereas AGILE 3 + < 0.45 and AGILE 4 < 0.25 were considered a rule-out. Results: 1244 subjects were included in the final analysis. The Median age was 53 (51.4–54.6) years, 55.6% were male, median BMI was 33.8 kg/m2 and 41.1% had T2DM. Based on AGILE 3+, 80.3% of the MASLD population were at low risk for AF and 11.5% were in grey zone. The prevalence of AF due to MASLD was 8.1% corresponding to 4.5 million Americans. Based on AGILE 4 score, 96.5% of the MASLD population were at low risk for cirrhosis and 2.4% were in the grey zone. The prevalence of MASLD-cirrhosis was 1.1% corresponding to 610,000 Americans. Conclusion: Our results suggest that approximately 4.5 million people in the U.S. have AF and 0.6 million have cirrhosis due to MASLD. [ABSTRACT FROM AUTHOR]

Background & Aims: Growing evidence suggests an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of immune-mediated inflammatory diseases (IMIDs). We aimed to clinically and mechanistically characterize steatotic liver disease (SLD) in a prospective cohort of patients with IMID compared to controls. Methods: Cross-sectional, case-control study including a subset of patients with IMID. Controls from the general population were age-, sex-, type 2 diabetes-, and BMI-matched at a 1:2 ratio. SLD was established using controlled attenuation parameter. Liver biopsies were obtained when significant liver fibrosis was suspected. Total RNA was extracted from freshly frozen cases and analyzed by RNA-seq. Differential gene expression was performed with ‘limma-voom’. Gene set-enrichment analysis was performed using the fgsea R package with a preranked “limma t-statistic” gene list. Results: A total of 1,456 patients with IMID and 2,945 controls were included. Advanced SLD (liver stiffness measurement ≥9.7 kPa) (13.46% vs. 3.79%; p

Background & aimsA two-step strategy combining a serum marker and magnetic resonance elastography (MRE) for detecting advanced fibrosis (stage 3-4) among patients with nonalcoholic fatty liver disease (NAFLD) has been proposed, but its diagnostic accuracy has not been evaluated. In this multicenter study, we aimed to investigate the diagnostic accuracy of a two-step strategy including Fibrosis-4 (FIB-4) followed by MRE.MethodsIn this multicenter study, 806 patients with biopsy-proven NAFLD who underwent contemporaneous MRE were enrolled and randomly assigned to training and validation cohorts. As a first step, patients with FIB-4

Introduction: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. Methods: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3–4). Results: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. Conclusion: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required. [ABSTRACT FROM AUTHOR]

Purpose: The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile. Materials and Methods: This is a retrospective study of a prospectively collected registry of patients with MASLD and compensated advanced chronic liver disease (cACLD) who underwent EGR. Patients were categorized as (1) monotherapy: EGR alone and (2) combination therapy: GLP-1RA prescribed within 6 months prior to or after EGR. Outcomes included changes in noninvasive tests of hepatic fibrosis, weight profile, and insulin resistance status at 12 months. Results: Thirty patients (body mass index 40.7 ± 9.3 kg/m2) were included. Of these, 12 patients (40%) underwent EGR monotherapy, and 18 patients (60%) underwent EGR + GLP-1RA combination therapy. Combination therapy group experienced greater improvements in fibrosis compared to monotherapy group (alanine aminotransferase: reduction by 55 ± 23% vs 29 ± 22% (p = 0.008), NAFLD fibrosis score: reduction by 181 ± 182% vs 30 ± 83% (p = 0.04), liver stiffness measurement on transient elastography: reduction by 54 ± 12% vs 14 ± 45% (p = 0.05)). There were greater reductions in hemoglobin A1c and homeostatic model assessment for insulin resistance in combination therapy compared to monotherapy (p < 0.05). At 12 months, the combination therapy group experienced 18.2 ± 6.6% TWL, while monotherapy group experienced 9.6 ± 3.3% TWL (p = 0.004). Conclusions: In patients with MASLD and cACLD, combination of EGR with GLP-1RA is associated with greater improvements in hepatic fibrosis, weight profile, and insulin resistance compared to EGR alone. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis‐4 (FIB‐4), gamma‐glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction‐associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3‐4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. Method: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. Results: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. Conclusions: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group. [ABSTRACT FROM AUTHOR]

Background/Aims Opinions differ regarding vibration-controlled transient elastography and magnetic resonance elastography (VCTE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of VCTE and MRE for diagnosing AF. Methods Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating VCTE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for VCTE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results A total of 19,199 patients from 63 studies using VCTE showed diagnostic AUC of 0.83 (95% confidence interval: 0.80–0.86), 0.83 (0.80–0.86), 0.87 (0.84–0.90), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89 (0.86–0.92), 0.92 (0.89–0.94), 0.89 (0.86–0.92), and 0.94 (0.91–0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. The diagnostic AUC for AF using VCTE was highest at 0.90 with a cut-off of 7.1–7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62–3.8 kPa. Conclusions VCTE (7.1–7.9 kPa) and MRE (3.62–3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.

Background: Information on the relation of air pollution with non-alcoholic fatty liver disease (NAFLD) is scarce. We thus conducted a large cross-sectional study in Asia to investigate the role of air pollution in NAFLD. Methods: We recruited 329,048 adults (mean age: 41.0 years) without other liver disease (hepatitis and cirrhosis) or excessive alcohol consumption in Taiwan and Hong Kong from 2001 to 2018. The concentrations of nitrogen dioxide (NO2) and ozone (O3) were estimated using a space–time regression model, and the concentrations of fine particulate matter (PM2.5) was evaluated using a satellite-based spatio-temporal model. NAFLD was determined using either the fatty liver index (FLI) or the hepatic steatosis index (HSI). The NAFLD-related advanced fibrosis was defined according to BARD score or the fibrosis-4 (FIB-4). A logistic regression model was adopted to explore the relationships of ambient air pollution with the odds of NAFLD and NAFLD-related advanced fibrosis. Results: We found positive relationships between PM2.5 and the odds of NAFLD and advanced fibrosis, with every standard deviation (SD, 7.5 µg/m3) increases in PM2.5 exposure being associated with a 10% (95% confidence interval [CI]: 9%–11%) increment in the prevalence of NAFLD and an 8% (95% CI: 7%–9%) increment in the prevalence of advanced fibrosis. Similarly, the prevalence of NAFLD and advanced fibrosis increased by 8% (95% CI: 7%–9%) and 7% (95% CI: 6%–8%) with per SD (18.9 µg/m3) increasement in NO2 concentration, respectively. Additionally, for every SD (9.9 µg/m3) increasement in O3 concentration, the prevalence of NAFLD and advanced fibrosis decreased by 12% (95% CI: 11%–13%) and 11% (95% CI: 9%–12%), respectively. Conclusion: Higher ambient PM2.5 and NO2 are linked with higher odds of NAFLD and advanced fibrosis. Our findings indicate that reducing PM2.5 and NO2 concentrations may be an effective way for preventing NAFLD. Further studies on O3 are warranted.

Background & Aims: aMAP score, as a hepatocellular carcinoma risk score, is proven to be associated with the degree of chronic hepatitis B‐related liver fibrosis. We aimed to evaluate the ability of aMAP score for metabolic dysfunction‐associated steatotic liver disease (MASLD; formerly NAFLD)‐related fibrosis diagnosis and establish a machine‐learning (ML) model to improve the diagnostic performance. Methods: A total of 946 biopsy‐proved MASLD patients from China and the United States were included in the analysis. The aMAP score, demographic/clinical indices and liver stiffness measurement (LSM) were included in seven ML algorithms to build fibrosis diagnostic models in the training set (N = 703). The performance of ML models was evaluated in the external validation set (N = 125). Results: The AUROCs of aMAP versus fibrosis‐4 index (FIB‐4) and aspartate aminotransferase‐platelet ratio (APRI) in cirrhosis and advanced fibrosis were (0.850 vs. 0.857 [P = 0.734], 0.735 [P = 0.001]) and (0.759 vs. 0.795 [P = 0.027], 0.709 [P = 0.049]). When using dual cut‐off values, aMAP had a smaller uncertainty area and higher accuracy (26.9%, 86.6%) than FIB‐4 (37.3%, 85.0%) and APRI (59.0%, 77.3%) in cirrhosis diagnosis. The seven ML models performed satisfactorily in most cases. In the validation set, the ML model comprising LSM and 5 indices (including age, sex, platelets, albumin and total bilirubin used in aMAP calculator), built by logistic regression algorithm (called LSM‐plus model), exhibited excellent performance. In cirrhosis and advanced fibrosis detection, the LSM‐plus model had higher accuracy (96.8%, 91.2%) than LSM alone (86.4%, 67.2%) and Agile score (76.0%, 83.2%), respectively. Additionally, the LSM‐plus model also displayed high specificity (cirrhosis: 98.3%; advanced fibrosis: 92.6%) with satisfactory AUROC (0.932, 0.875, respectively) and sensitivity (88.9%, 82.4%, respectively). Conclusions: The aMAP score is capable of diagnosing MASLD‐related fibrosis. The LSM‐plus model could accurately identify MASLD‐related cirrhosis and advanced fibrosis. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (<55 U/L) who may remain undetected. We investigated the clinical implications of a lower ALT cut-off (>30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. Materials and Methods: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31-41 U/L, 42-54 U/L and =55 U/L were compared. Results: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31 -41 U/L, 31 (18 %) had ALT 42-54 U/L and 116 (69 %) had ALT =55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31-41 U/L, 28 (19 %) had ALT 42-54 U/L and 97 (67 %) had ALT =55 U/L. Conclusions: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31-54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care. [ABSTRACT FROM AUTHOR]

Achieving a sustained virologic response (SVR) through direct-acting antivirals for hepatitis C virus (HCV) infection significantly reduces the long-term risk of hepatocellular carcinoma (HCC), particularly in patients with advanced fibrosis (F3) or cirrhosis (F4). However, despite this improvement, the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate. This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively, especially at advanced fibrosis (F3), and the unclear cost-effectiveness, modality, frequency, and duration of HCC surveillance in individuals with SVR but without cirrhosis. These factors contribute to significant variations in surveillance guidelines recommended by different professional societies. Therefore, there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians. This review article evaluates the existing data, addresses ongoing controversies, and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients with type 2 diabetes (T2D) have a high prevalence of non-alcoholic fatty liver disease (NAFLD) (55%) and are at increased risk for developing non-alcoholic steatohepatitis, a severe form of NAFLD. Early detection of advanced fibrosis in patients with T2D and NAFLD is crucial and can prevent progression to chronic liver disease, cirrhosis, and hepatocellular carcinoma. However, screening for liver disease and risk-stratification pathways are not established in patients with T2D. We evaluated the efficacy of using the automated fibrosis-4 (FIB-4) index in routine clinical settings to identify patients requiring further specialist evaluation. Materials and Methods: In this prospective cohort study, individuals diagnosed with T2D were recruited from diabetes clinics at a tertiary university hospital. Demographic, clinical, and laboratory data were comprehensively collected. The FIB-4 index was automatically calculated and integrated into the hospital’s electronic medical records (EMRs), which were then stratified by age. Patients with advanced fibrosis (FIB-4 index ≥ 1.3) were referred to a specialist. Student’s t-test or the Mann–Whitney U test was used to analyze variables associated with advanced fibrosis. Logistic regression was used to identify predictors of advanced fibrosis. Results: Among the 318 patients with T2D, 9.7% had advanced fibrosis. The majority were females (54.7%) and Saudi nationals (89.6%). Several factors, including age, platelet count, total bilirubin, serum albumin, total cholesterol, low-density lipoprotein, transaminases, and gamma-glutamyl transferase (GGT), showed significant associations with advanced fibrosis (all p < 0.05). Older age, elevated total bilirubin and GGT levels, and prolonged international normalized ratio emerged as independent predictors of advanced fibrosis. Conclusions: Integrating the FIB-4 index into the EMR during the routine care of patients with T2D proved to be a valuable tool in effectively identifying individuals at risk of advanced fibrosis. Our findings emphasize the need for further research to refine screening strategies in this high-risk population.

Introduction and Objectives: Early diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD), especially with advanced fibrosis, is crucial due to the increased risk of complications and mortality. Serum alanine aminotransferase (ALT) is commonly used; however, many patients have normal ranges (30 U/L) using intelligent liver function testing (iLFT) to identify MASLD patients with and without advanced fibrosis in primary care. Materials and Methods: All patients entering the iLFT diagnostic pathway had liver aetiological screening investigations if ALT >30 U/L. In those with MASLD the proportions with and without advanced fibrosis at different ALT thresholds: 31–41 U/L, 42–54 U/L and ≥55 U/L were compared. Results: 16,373 patients underwent iLFT between March 2016 to April 2022. 762 (5 %) patients had MASLD with abnormal fibrosis scores, while 908 (6 %) had MASLD with normal fibrosis scores. 428 (56 %) patients were assessed in liver clinics, where 169 (39 %) had evidence of fibrosis. Of these, 22 (13 %) had ALT 31–41 U/L, 31 (18 %) had ALT 42–54 U/L and 116 (69 %) had ALT ≥55 U/L. 145 (86 %) patients had advanced fibrosis or cirrhosis, where 20 (14 %) had ALT 31–41 U/L, 28 (19 %) had ALT 42–54 U/L and 97 (67 %) had ALT ≥55 U/L. Conclusions: 33 % of MASLD patients with advanced fibrosis or cirrhosis had ALT 31–54 U/L, who would have been missed using the conventional ALT range. This suggests that lowering the ALT cut-off improves diagnosis of MASLD with advanced fibrosis in primary care.

Background and aimA high aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is associated with liver injury in liver disease; however, no data exist regarding its relationship with 90-day prognosis in patients with acute exacerbation of chronic liver disease.MethodsIn this study, 3,758 participants (955 with advanced fibrosis and 2,803 with cirrhosis) from the CATCH-LIFE cohort in China were included. The relationships between different AST/ALT ratios and the risk of adverse 90-day outcomes (death or liver transplantation) were determined in patients with cirrhosis or hepatitis B virus (HBV)-associated advanced fibrosis, respectively.ResultsIn the patients with HBV-associated advanced fibrosis, the risk of 90-day adverse outcomes increased with AST/ALT ratio; after adjusting for all confounding factors, the risk of adverse 90-day outcomes was the highest when AST/ALT ratio was more than 1.08 (OR = 6.91 [95% CI = 1.789–26.721], p = 0.005), and the AST/ALT ratio of >1.9 accelerated the development of adverse outcomes. In patients with cirrhosis, an AST/ALT ratio > 1.38 increased the risk of adverse 90-day outcomes in all univariables (OR = 1.551 [95% CI = 1.216–1.983], p 1.38 corresponded with a more than 20% incidence of adverse outcomes in patients with cirrhosis.ConclusionThe AST/ALT ratio is an independent risk factor for adverse 90-day outcomes in patients with cirrhosis and HBV-associated advanced fibrosis. The cutoff values of the AST/ALT ratio could help clinicians monitor the condition of patients when making clinical decisions.

Introduction: Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10–20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. Methods: We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. Results: ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. Conclusions: Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme. [ABSTRACT FROM AUTHOR]

Summary: Background: No prospective diagnostic studies have directly compared widespread non‐invasive liver tests in patients with type 2 diabetes (T2D) using the intention‐to‐diagnose method for each of the three main histological features of metabolic dysfunction associated steatotic liver disease ‐ namely fibrosis, metabolic dysfunction‐associated steatohepatitis (MASH), and steatosis. Aims: To compare the performance of nine tests using the intention‐to‐diagnose rather than the standard method, which would exclude non‐evaluable participants Methods: Biopsy was used as the reference with predetermined cut‐offs, advanced fibrosis being the main endpoint. The Nash‐FibroTest panel including FibroTest‐T2D, SteatoTest‐T2D and MashTest‐T2D was optimised for type 2 diabetes. FibroTest‐T2D was compared to vibration‐controlled transient elastography stiffness (VCTE), two‐dimensional shear‐wave elastography stiffness (TD‐SWE), and Fibrosis‐4 blood test. NashTest‐T2D was compared to aspartate aminotransferase. SteatoTest‐T2D was compared to the controlled attenuation parameter and the hepatorenal gradient. Results: Among 402 cases, non‐evaluable tests were 6.7% for VCTE, 4.0% for hepatorenal gradient, 3.2% for controlled attenuation parameter, 1.5% for TD‐SWE, 1.2% for NashTest‐T2D, and 0.02% for Fibrosis‐4, aspartate aminotransferase and SteatoTest‐T2D. The VCTE AUROC for advanced fibrosis was over‐estimated by 6% (0.83 [95% CI: 0.78–0.87]) by standard analysis compared to intention‐to‐diagnose (0.77 [0.72–0.81] p = 0.008). The AUROCs for advanced fibrosis did not differ significantly in intention‐to‐diagnose between FibroTest‐T2D (0.77; 95% CI: 0.73–0.82), VCTE (0.77; 95% CI: 0.72–0.81) and TD‐SWE(0.78; 0.74–0.83) but were all higher than the Fibrosis‐4 score (0.70; 95% CI all differences ≥7%; p ≤ 0.03). For MASH, MashTest‐T2D had a higher AUROC (0.76; 95% CI: 0.70–0.80) than aspartate aminotransferase (0.72; 95% CI: 0.66–0.77; p = 0.035). For steatosis, AUROCs did not differ significantly between SteatoTest‐T2D, controlled attenuation parameter and hepatorenal gradient. Conclusions: In intention‐to‐diagnose analysis, FibroTest‐T2D, TD‐SWE and VCTE performed similarly for staging fibrosis, and out‐performed Fibrosis‐4 in outpatients with type 2 diabetes. The standard analysis over‐estimated VCTE performance. ClinicalTrial.gov: NCT03634098. [ABSTRACT FROM AUTHOR]

Background: The impact of non‐alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality. Methods: The study population consisted of 137 206 participants from Constances cohort. Non‐invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver‐related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all‐cause mortality. Results: The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW‐weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01–1.57), hepatic‐related complications (HR 2.48, 95% CI 1.99–3.29), CVD (HR 1.42, 95% CI 1.30–1.55), EHC (HR 1.11, 95% CI 1.01–1.28) and CKD (HR 1.81, 95% CI 1.53–2.07) compared to those without chronic liver diseases risk factors (Non‐NAFLD). In the trend analysis over the study period of inclusion and compared to Non‐NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07–1.76 per year), CVD (HR 1.08, 95% CI 1.03–1.12), CKD (HR 1.16, 95% CI 1.07–1.25), and death (HR 1.39, 95% CI 1.39–1.50). Conclusion: This large community‐based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest‐growing trend. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) is the main condition of altered liver enzymes worldwide. With a constant increase in liver hospitalizations, MAFLD is the second cause of cirrhosis and soon will be the first cause of liver transplantation. Early recognition of MAFLD and a personalized approach are essential to its treatment. This case study presents personalized management of a patient with MAFLD with advanced fibrosis and severe steatosis. The impact of silymarin use, concomitant treatment with diet, exercise, insulin sensitizers and antifibrotic agents, was evaluated. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series

Background & Aims: Non‐alcoholic fatty liver disease (NAFLD) and the newly proposed metabolic‐associated fatty liver disease (MAFLD) were each associated with subclinical atherosclerosis. However, there is limited evidence on risk of atherosclerosis in individuals who meet the criteria for one but not the other. We aimed to investigate the associations of MAFLD or NAFLD status with site‐specific and multiple‐site atherosclerosis. Methods: This is a prospective cohort study involving 4524 adults within the MJ health check‐up cohort. Logistic regression model was used to estimate odds ratios (ORs) and confidence intervals (CIs) for subclinical atherosclerosis (elevated carotid intima‐media thickness [CIMT], carotid plaque [CP], coronary artery calcification [CAC] and retinal atherosclerosis [RA]) associated with MAFLD or NAFLD status, MAFLD subtypes and fibrosis status. Results: MAFLD was associated with higher risks of elevated CIMT, CP, CAC and RA (OR: 1.41 [95% CI 1.18–1.68], 1.23 [1.02–1.48], 1.60 [1.24–2.08], and 1.79 [1.28–2.52], respectively), whereas NAFLD per se did not increase risk of atherosclerosis except for elevated CIMT. Individuals who met both definitions or the definition for MAFLD but not NAFLD had higher risk of subclinical atherosclerosis. Among MAFLD subtypes, MAFLD with diabetes had the highest risk of subclinical atherosclerosis, but the associations did not differ by fibrosis status. Stronger positive associations were observed of MAFLD with multiple‐site than single‐site atherosclerosis. Conclusions: In Chinese adults, MAFLD was associated with subclinical atherosclerosis, with stronger associations for multiple‐site atherosclerosis. More attention should be paid to MAFLD with diabetes, and MAFLD might be a better predictor for atherosclerotic disease than NAFLD. [ABSTRACT FROM AUTHOR]

Objective: The risk of nonalcoholic fatty liver disease (NAFLD) is increased significantly in individuals having Type 2 diabetes mellitus (T2DM) and the presence of T2DM enormously drives NAFLD progression. However, in clinical practice, it is overlooked despite the significant clinical effects of NAFLD in T2DM. Our study aimed to estimate the prevalence of NAFLD in T2DM patients from the eastern region of India. Methods: This cross-sectional study assessed 132 T2DM patients for NAFLD. Anthropometry and lipid estimations were done in all the individuals. Hepatic fibrosis was diagnosed by transient elastography (TE) using a TOUCH 502 Fiber Scanner using M‑probe. A fibrosis score ≥ 11 kgpascals (kPa) was used to define advanced fibrosis (F3). Results: Overall prevalence of NAFLD in T2DM patients was 57% (75/132 subjects) and the prevalence is higher in males (54.6%). Results showed that approximately 26% of patients with NAFLD will develop into NASH, among them 37.3% developed mild to moderate steatosis and 26.6% developed severe steatosis. Conclusion: The prevalence of NAFLD is high in the eastern region of India, need for early diagnosis and treatment of NAFLD in T2DM. The use of TE with other serum markers can be helpful for the diagnosis of advanced fibrosis.

Background: As recommendations for non-invasive fibrosis risk assessment in nonalcoholic fatty liver disease (NAFLD) emerge, it is not known how often they are performed in primary care. Aims: We investigated the completion of confirmatory fibrosis risk assessment in primary care patients with NAFLD and indeterminate-risk or greater Fibrosis-4 Index (FIB-4) and NAFLD Fibrosis Scores (NFS). Methods: This retrospective cohort study of electronic health record data from a primary care clinic identified patients with diagnoses of NAFLD from 2012 through 2021. Patients with a diagnosis of a severe liver disease outcome during the study period were excluded. The most recent FIB-4 and NFS scores were calculated and categorized by advanced fibrosis risk. Charts were reviewed to identify the outcome of a confirmatory fibrosis risk assessment by liver elastography or liver biopsy for all patients with indeterminate-risk or higher FIB-4 (≥ 1.3) and NFS (≥ − 1.455) scores. Results: The cohort included 604 patients diagnosed with NAFLD. Two-thirds of included patients (399) had a FIB-4 or NFS score greater than low-risk, 19% (113) had a high-risk FIB-4 (≥ 2.67) or NFS (≥ 0.676) score, and 7% (44) had high-risk FIB-4 and NFS values. Of these 399 patients with an indication for a confirmatory fibrosis test, 10% (41) underwent liver elastography (24) or liver biopsy (18) or both (1). Conclusions: Advanced fibrosis is a key indicator of future poor health outcomes in patients with NAFLD and a critical signal for referral to hepatology. Significant opportunities exist to improve confirmatory fibrosis risk assessment in patients with NAFLD. [ABSTRACT FROM AUTHOR]

Abstract Background Testosterone has an impact on metabolic disorders and men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism; meanwhile, patients with T2DM have higher risk of NAFLD. Therefore, we speculate that testosterone may affect the progression of NAFLD in T2DM patients and we aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM. Methods A cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable). Results In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95% CI 1.31–3.28, P for trend = 0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72–0.92, P for trend

Background: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver‐related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non‐invasive tests (NITs) including FIB‐4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. Aim: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. Methodology: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. Results: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62–0.69) for FIB‐4 and 0.63 (95% CI 0.60–0.66) for APRI. The specificities were 0.94 for FIB‐4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63–0.71) for FIB‐4, 0.60 (95% CI 0.56–0.64) for APRI and 0.65 (95% CI 0.61–0.69) for NFS. The specificities were 0.95 for FIB‐4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. Conclusion: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB‐4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects. [ABSTRACT FROM AUTHOR]

Clin Gastroenterol Hepatol 2019; 17 (06): 1148-1156.e4 43 McPherson S, Stewart S F, Henderson E, Burt A D, Day C P. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. J Hepatol 2013; 59 (02): 236-242 51 Vali Y, Lee J, Boursier J LITMUS Systematic Review Team Enhanced liver fibrosis test for the non-invasive diagnosis of fibrosis in patients with NAFLD: a systematic review and meta-analysis. However, only a fraction of patients with NAFLD ultimately develop cirrhosis or decompensated liver disease, and the natural history is highly heterogeneous: a small number of "fast progressors" develop cirrhosis rapidly, others experience fibrosis progression along a predictable trajectory, and still others may have seemingly spontaneous regression of fibrosis. Keywords: noninvasive tests; NIT; advanced fibrosis; cirrhosis; NASH EN noninvasive tests NIT advanced fibrosis cirrhosis NASH 133 141 9 07/18/23 20230501 NES 230501 Lay Summary Finding patients with nonalcoholic fatty liver disease who are at high risk of developing advanced liver disease is recommended in certain patient populations. [Extracted from the article]

Aim: The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan. Methods: We analyzed 371 Japanese patients with biopsy‐proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac‐2‐binding protein glycosylation isomer (M2BPGi), the Fibrosis‐4 (FIB‐4) index, and combinations of these indices. Results: In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1–4, F0–1 versus F2–4, F0–2 versus F3–4, and F0–3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB‐4 index and M2BPGi at each fibrosis stage. Respective low and high cut‐off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB‐4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%. Conclusions: In Japan, the ELF test predicts NAFLD‐related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate. [ABSTRACT FROM AUTHOR]