Search Results (150)

Multiple North American and European societies now endorse a combined serological and imaging-based clinical care pathway for non-invasive risk stratification of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A multidisciplinary group of Canadian radiologists, hepatologists, family physicians, and other health professionals have recently published consensus guidelines for identification and risk stratification of patients with suspected MASLD. Screening should be performed with the FIB-4 score, and those with an indeterminate FIB-4 (between 1.32.67) should undergo imaging-based liver stiffness evaluation either with transient elastography (FibroScan), ultrasound shear wave elastography, or magnetic resonance elastography as a second step. While the implementation of these techniques for measuring liver stiffness differ, there is no clinically significant difference in their diagnostic performance. This narrative review, intended for Family Physicians, summarizes recommendations for serological investigations and imaging modalities of liver steatosis and stiffness. Practical guidance includes an algorithm with thresholds. We discuss current challenges and future directions of risk-stratifying patients with MASLD in the community. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with obesity, insulin resistance, and altered body composition. Although dietary intervention is a cornerstone of treatment, complex or calorie-restricted regimens may reduce long-term adherence. This study evaluated the effects of a pragmatic, short-term intervention that involved replacing one daily carbohydrate serving with cruciferous vegetables on body composition and metabolic parameters in individuals with obesity and MASLD. Associations between changes in fat mass and vitamin D and follistatin levels were also explored. Methods: In this prospective pilot study, 44 adults with obesity and MASLD followed a two-month intervention, substituting one daily serving of carbohydrate-rich foods with 200 g of cruciferous vegetables, without prescribed caloric restriction. Anthropometric, bioimpedance, biochemical, and FibroScan assessments were performed at baseline and post-intervention. Changes were analyzed using the Wilcoxon signed-rank test, Spearman’s correlation analysis, and generalized estimating equation (GEE) models adjusted for confounding factors. Results: The intervention was associated with a significant reduction in fat mass (−4.86 kg, p < 0.001), corresponding to an average relative decrease of approximately 12% along with improvements in metabolic and hepatic parameters. Changes in fat mass were inversely correlated with changes in vitamin D (rho = −0.33, p = 0.035), fat-free mass (rho = −0.37, p = 0.018), and follistatin (rho = −0.24, p = 0.143). In multivariate GEE models, the intervention remained independently associated with fat mass reduction (β = −5.190, p < 0.001). Conclusions: A simple carbohydrate-to-vegetable substitution without prescribed caloric restriction was associated with improvements in body composition and metabolic health. These exploratory findings suggest that pragmatic dietary modifications may provide clinically meaningful metabolic benefits and support the feasibility of minimal dietary substitution strategies in this population. However, causal inferences remain limited by a single-arm pilot design and require confirmation in larger randomized controlled trials. Full article

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased rapidly in pediatric populations. Evidence on the cost-effectiveness of pediatric MASLD screening strategies remains limited. Methods: A decision tree combined with a Markov state-transition model was developed to evaluate the cost-effectiveness of three WHtR-based two-stage screening strategies among children aged 6–14 years in Beijing, China: WHtR combined with ultrasound (S1), WHtR combined with FibroScan^® (S2), and WHtR combined with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) (S3), compared with no screening (S4). All screening strategies were combined with lifestyle modification programs, including dietary and exercise management. Model inputs were derived from the published literature, national survey data, and expert consensus. Costs and quality-adjusted life years (QALYs) were estimated from a healthcare system perspective over a 10-year time horizon, with a 3% annual discount rate. Incremental cost–utility ratios (ICURs) were calculated, and extensive one-way, two-way, and probabilistic sensitivity analyses were performed. Results: Our model indicated that, at a willingness-to-pay (WTP) threshold of $30,584.0 per QALY, corresponding to three times the gross domestic product (GDP) per capita of China, S2 was identified as the optimal strategy. At a higher WTP threshold of $71,415.5 per QALY, based on the GDP per capita of Beijing, S3 became the most cost-effective option. All three screening strategies were more cost-effective than no screening across both thresholds. Sensitivity analyses demonstrated that utility values for fibrosis stages and the response rate of the lifestyle modification program were the most influential parameters, and probabilistic sensitivity analysis confirmed the robustness of the baseline findings. Conclusions: To the best of our knowledge, this is the first cost-effectiveness analysis for pediatric MASLD in China. Model-based estimates suggest that early screening for MASLD in children using WHtR-based screening strategies is cost-effective, with FibroScan^® preferred in settings with average economic development and MRI-PDFF preferred in more affluent regions. These findings underscore the importance of context-specific implementation of early MASLD screening strategies in pediatric populations to mitigate long-term disease burden. Full article

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54–92% of patients and normalization of alanine transaminase (ALT) in 48.8–74% of patients after 23–144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance. Full article

Hepatitis delta (HDV) infection affects 5% of hepatitis B (HBV)-positive patients and is associated with an increased risk of cirrhosis and hepatocellular carcinoma; however, it remains underdiagnosed. The first part of our Delta Describe study highlights the insufficient level of HDV screening among patients in metropolitan France. In this study, we report on their real-world management. Patients with at least one positive HDV RNA test performed in 2019 were identified through the major public and private laboratories in France. From January 2024 to July 2025, informed patients were interviewed, and physicians supplemented the collected data. A total of 547 patients were included, with a median age of 44 years; most originated from Africa or Eastern Europe. HIV and hepatitis C coinfections were reported in 15.2% and 4.6% of patients, respectively. Liver fibrosis was primarily assessed using FibroScan^®. Most patients knew the year of their delta diagnosis, and 69.1% knew their fibrosis stage. Liver-related events occurred in 14.3% (67/468) of patients, mainly comprising portal hypertension (61.6%), liver failure (12.3%), and hepatocellular carcinoma (26%), and 45 patients (45/468) underwent liver transplantation. At the time of the survey, 47.1% of the patients reported undetectable HDV RNA; 40.6% (222/547) had currently or previously undergone BLV treatment. Among patients receiving ongoing treatment for HDV at the time of the survey, 84.8% were receiving nucleos(t)ide analogs (NUCs). In metropolitan France, HDV patients had access to specialized follow-up care and innovative therapies (bulevirtide), were mostly on NUCs, and demonstrated good disease awareness. Full article

Background: Severe Alpha-1-Antitrypsin deficiency (AATD), phenotype PiZZ, is a leading cause of liver disease in neonates, children, and adults. Nevertheless, the prevalence of liver disease and mortality within PiZZ adults remains unclear. Between 1972 and 1974, a cohort of 129 individuals with severe AATD (PiZZ) was identified through the Swedish national screening of 200,000 newborns. The cohort has been followed up regularly since birth. This prospective cohort follow-up study, with a cross-sectional comparison at 50 years of age, aims to characterize the natural history of liver disease and mortality in this cohort in their early fifties, compared with an age-matched control group (PiMM) randomly selected from the population registry. Methods: Study participants completed questionnaires regarding occupation, medical history, medication, and alcohol consumption. They underwent physical examination and measurement of liver stiffness using transient elastography (TE, FibroScan^®). Blood samples were obtained for evaluation of liver function, alcohol consumption, calculation of liver fibrosis scores, and detection of viral hepatitis and autoimmune liver disease. Results: Ninety-five PiZZ and 124 PiMM individuals participated in the study, of whom 47 PiZZ and 96 PiMM underwent TE measurement. PiZZ individuals had significantly higher median liver stiffness compared with PiMM individuals (5.9 kPa vs. 4.5 kPa, p < 0.01). No significant differences were found in Fib-4 score or the Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) between the groups. Since identification of the cohort at birth, 13 (10%) of the 129 PiZZ individuals have died. Of these, liver disease was the main or underlying cause of death in 8 individuals (6%). Conclusions: In their early fifties, PiZZ individuals show a small but significant increase in liver stiffness measured by TE, indicating early liver fibrosis. In contrast, conventional fibrosis scores, such as Fib-4 and NFS, do not differ between PiZZ individuals and PiMM, suggesting that serum-based fibrosis scores may underestimate fibrosis in AATD. In this cohort, liver disease and its complications represented the main cause of death in PiZZ individuals by the age of 50, an observation that is uncommon in the general population at this age. Full article

Background/Objectives: This observational study investigated associations between human leukocyte antigen (HLA) polymorphisms and imaging-defined hepatic steatosis (non-alcoholic fatty liver disease—NAFLD) and liver fibrosis in patients with rheumatoid arthritis (RA). Methods: Steatosis was assessed by transient elastography (FibroScan) and defined as controlled attenuation parameter (CAP) ≥ 275 dB/m; fibrosis was defined as liver stiffness measurement ≥ 8 kPa. We tested 11 frequent HLA alleles (HLA-A*02, HLA-B*07, HLA-B*08, HLA-B*27, HLA-B*35, HLA-B*44, HLA-B*51, HLA-DRB1*11, HLA-DRB1*14, HLA-DRB1*15, and HLA-DRB1*16). Associations were evaluated using multivariable logistic regression (individual and omnibus models) adjusted for age, body mass index (BMI), triglycerides, and glucose. Results: A total of 176 patients with rheumatoid arthritis were enrolled. NAFLD/steatosis was present in 35.2% of patients (n = 62), and fibrosis in 10.8% (n = 19). No HLA allele was significantly associated with steatosis or fibrosis after correction for multiple testing. BMI and triglycerides were independently associated with steatosis (BMI OR 1.22, 95% CI 1.12–1.34; triglycerides OR 1.48, 95% CI 1.04–2.18). For fibrosis, HLA-DRB1*15 showed the strongest trend-level association (OR ~2.6–2.9) but did not remain significant after correcting for multiple testing. Conclusions: In this RA cohort, metabolic factors (particularly BMI and triglycerides) were the dominant predictors of CAP-defined steatosis. No robust association between the tested HLA markers and steatosis or fibrosis was identified. Trend-level signals—most notably HLA-DRB1*15 for fibrosis—should be considered hypothesis-generating and warrant replication in larger, adequately powered cohorts. Full article

Background: Pediatric hepatitis C virus (HCV) infection is often asymptomatic but may lead to significant liver disease later in life. In Romania, data on pediatric HCV remains scarce. This study aimed to describe the clinical and epidemiological characteristics of children with chronic HCV infection in a Romanian cohort. Methods: We conducted a retrospective study that included 83 pediatric patients evaluated for chronic hepatitis C between 1995 and 2024 at a tertiary pediatric hospital from Bucharest, Romania. Demographic data, routes of transmission, biochemical parameters, viral load, and liver fibrosis assessed by FibroScan^® or liver biopsy were analyzed. Results: The median age at diagnosis was 73 months (IQR 36–156), with a slight female predominance (54.2%). Vertical transmission was the most common (48.2%). Most children had normal or mildly elevated transaminases at diagnosis. Although pediatric HCV hepatic involvement is generally considered mild, in our cohort only 40.6% of children had absent or mild fibrosis at diagnosis, while in 33.7% of cases moderate fibrosis was identified, and 8.4% had severe fibrosis or cirrhosis. No significant correlations were found between viral load, transaminase levels, and fibrosis severity. Conclusions: Pediatric HCV infection in Romania is frequently diagnosed late, mainly due to the lack of systematic perinatal screening. Although liver disease is generally mild, the cases of advanced fibrosis highlight the need for early diagnosis and improved screening strategies. Full article

Metabolic dysfunction associated steatotic liver disease (MASLD), a globally prevalent chronic liver disease, has only limited pharmacological options. Both metformin and Ganwei, health supplements containing a potent inducer of glycine N-methyltransferase (GNMT), have shown great promise for the treatment of MASLD. We conducted a 4-arm, randomized, placebo-controlled trial to investigate the safety and efficacy of metformin and Ganwei for patients with MASLD. Between September 2021 and March 2023, 64 patients with MASLD were randomly assigned at a 1:1:1:1 ratio to receive metformin alone (arm A, n = 16), a combination of metformin and Ganwei (arm B, n = 16), a placebo alone (arm C, n = 16) or Ganwei alone (arm D, n = 16) for 6 months. The primary liver steatosis outcome was assessed by control attenuation parameter (CAP) and kilopascal (kPa) scores via FibroScan. The key secondary outcomes included safety, liver function and patients’ metabolic profiles. At 6 months after treatment, significant improvements in liver steatosis were observed in patients treated with Ganwei alone (repeated-measures ANOVA test, p = 0.048 and 0.048 for CAP and kPa scores, respectively) but not in patients treated with placebo and other arms. By employing a 6-point steatosis grade scale, the Ganwei alone arm exhibited a statistically significant improvement over the placebo-controlled arm (mean score 1.1 ± 1.8 vs. 0.1 ± 0.7, p = 0.036). Located in the promoter region of the GNMT gene, the SNP rs10948059 polymorphism is known to affect GNMT promoter activity. Interestingly, genotype analysis revealed that the improvement in liver steatosis in the Ganwei alone arm was restricted to patients harboring the T allele at GNMT rs10948059 (C/T and T/T vs. C/C, p < 0.05). No serious adverse events were observed in any of the treatment arms. Our study demonstrated that Ganwei may be an effective treatment option for MASLD patients. Improvement in liver steatosis by Ganwei was affected by GNMT promotor activity. Clinical trial registration: NCT06244550. Full article

Background & Aims: The accurate, noninvasive assessment of hepatic steatosis is essential in living liver donor evaluation, where disease prevalence is low, and donor safety is paramount. This study evaluated commonly used noninvasive diagnostic tools for detecting hepatic steatosis in a real-world donor screening setting. Methods: We analyzed 108 living liver donor candidates (18–53 years) with complete MRI, CT, transient elastography (FibroScan^®), and biochemical data obtained during routine donor evaluation. Hepatic steatosis was defined as an MRI-proton density fat fraction (PDFF) ≥5%, which served as the noninvasive reference standard. Diagnostic performance metrics, receiver operating characteristic (ROC) analyses, and correlations with serum fibrosis indices (FIB-4 and APRI) were assessed. Results: MRI-PDFF identified hepatic steatosis in 21 donors (19.4%). Controlled attenuation parameter (CAP), measured by transient elastography, demonstrated high sensitivity (90.5%) and negative predictive value (97.1%), supporting its role as a rule-out screening tool. CT showed excellent specificity (97.7%) but lower sensitivity (61.9%), consistent with a confirmatory role when MRI is unavailable. Serum fibrosis indices were generally low and did not correlate strongly with imaging-based steatosis. Conclusions: In the low-prevalence setting of living liver donor evaluation, CAP-based transient elastography provides effective noninvasive screening for hepatic steatosis, while MRI-PDFF serves as a confirmatory reference when indicated. These findings support a stepwise, clinically practical diagnostic approach that prioritizes donor safety and workflow efficiency. Full article

Background/Objectives: Obstructive sleep apnea (OSA) causes recurrent apneas/hypopneas and intermittent oxygen desaturation during sleep. Chronic intermittent hypoxia (CIH) may be linked to metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis through metabolic dysfunction. This study evaluated the relationship between OSA severity/hypoxemia indices and MASLD and fibrosis assessed by transient elastography. Methods: We prospectively enrolled 400 adults evaluated for suspected OSA at a respiratory disease outpatient clinic in Rize, Türkiye. All patients underwent overnight polysomnography. The apnea–hypopnea index (AHI), oxygen desaturation index (ODI), mean SpO₂, and mean of each participant’s minimum SpO₂ values were recorded. MASLD and fibrosis were assessed in the same individuals using FibroScan, with CAP (controlled attenuation parameter) and LSM (liver stiffness measurement) values recorded. OSA severity was categorized by AHI, and multivariable logistic regression was used to identify independent associations. Results: MASLD was present in 76% and fibrosis in 34.5% of patients. Patients with fibrosis had higher AHI (13.8 [8.2–35.2]) and ODI (11.5 [4.5–33.2]) and lower minimum SpO₂ (p < 0.001). In multivariable models, BMI (OR 1.09; p < 0.001) and metabolic syndrome (OR 3.34; p < 0.001) were independently associated with MASLD, while BMI (OR 1.02; p < 0.001), metabolic syndrome (OR 2.03; p = 0.015), and ALT (OR 1.02; p = 0.032) were independently associated with fibrosis. Conclusions: MASLD and fibrosis were associated with OSA severity and hypoxemia before multivariable adjustment. However, after adjustment for obesity-related factors, liver outcomes were primarily explained by BMI and metabolic syndrome. Liver assessment should be considered in patients with OSA, particularly in those with high BMI and metabolic syndrome. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a key contributor to the development of heart failure with preserved ejection fraction in individuals with obesity. This study aimed to investigate whether MASLD and diastolic dysfunction are independently associated with abdominal obesity through shared metabolic and oxidative mechanisms. We conducted a cross-sectional study in a tertiary university hospital including patients aged ≥ 50 years with obesity and MASLD. Clinical, anthropometric, biochemical, and oxidative stress parameters were collected, and hepatic steatosis and fibrosis were assessed using vibration-controlled transient elastography (FibroScan^®). Patients were stratified according to the presence or absence of echocardiographic diastolic dysfunction. A total of 73 patients was included in the analysis and 27.4% had diastolic dysfunction. Patients with diastolic dysfunction were older and had higher body weight, body mass index (BMI) and waist circumference. Markers of hepatic steatosis, including fatty liver index (FLI) and controlled attenuation parameter (CAP), were higher in patients with diastolic dysfunction, whereas fibrosis measures were not. CAP was independently associated with diastolic dysfunction after adjustment for age and sex, but this association was lost after further adjustment for waist circumference, suggesting a mediating role of central adiposity. Plasma glutathione was inversely associated with FLI, but oxidative stress markers were not associated with diastolic dysfunction or steatosis severity. In conclusion, in patients ≥ 50 years with MASLD and obesity, diastolic dysfunction was common and closely related to abdominal obesity, highlighting MASLD as a multisystem condition with early cardiac involvement. Full article

Background: Nonalcoholic fatty liver disease (NAFLD) is common in rheumatoid arthritis (RA), and methotrexate (MTX) use raises concern about hepatotoxicity. We evaluated whether HLA-DRB1, PNPLA3, SLCO1B1, and MTHFR variants are associated with NAFLD, liver fibrosis, or MTX toxicity/pharmacokinetics in RA, after accounting for clinical covariates. Methods: In a cross-sectional cohort of 159 patients with RA, NAFLD, and fibrosis were assessed by FibroScan (CAP ≥ 275 dB/m; LSM > 8 kPa). We compared baseline characteristics by NAFLD status and fitted multivariable models for NAFLD, fibrosis, ALT elevation, and MTX toxicity; MTX pharmacokinetics were analyzed in 111 MTX-treated patients. Multiple testing was controlled using the Benjamini–Hochberg method. Results: The prevalence of NAFLD was 36%, and that of fibrosis was 11%. NAFLD patients had higher CAP and LSM, and markedly greater adiposity indices (body weight, BMI, waist and hip circumference, WC). BMI and WC were independently associated with NAFLD (BMI OR 1.27 per kg/m², 95% CI 1.16–1.40; WC OR 1.06 per cm, 95% CI 1.01–1.12). No HLA-DRB1, PNPLA3, SLCO1B1, or MTHFR variant showed an association that survived multiple-comparison correction. Among MTX users, 21/111 (19%) experienced toxicity. SLCO1B1 and MTHFR variants did not influence MTX pharmacokinetics; age was associated with lower dose-normalized MTX exposure, and cumulative dose was positively associated with exposure. Conclusions: In RA, adiposity—not the tested candidate pharmacogenes—drives NAFLD risk, and SLCO1B1/MTHFR variants do not support MTX dose adjustment. The findings emphasize routine clinical risk factors over single-gene testing for NAFLD and MTX hepatotoxicity in this setting. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the greatest challenges for the modern public health system and serves as the foundation for the development of advanced stages, such as metabolic dysfunction-associated steatohepatitis (MASH), which may progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). MASLD and type 2 diabetes mellitus (T2DM) mutually exacerbate one another. MASLD increases the incidence of T2DM and the risk of complications in patients already affected. T2DM accelerates progression to MASH, which has become the second leading cause of liver transplantation and end-stage liver disease, and is associated with hepatic decompensation, cirrhosis, HCC, chronic kidney disease, and cardiovascular disease. MASLD and MASH are strongly linked to T2DM and obesity, pathogenesis including genetic polymorphisms, environmental factors, and multiple metabolic disturbances: insulin resistance (IR), gut dysbiosis, altered adipokine signaling, such as reduced adiponectin alongside increased pro-inflammatory cytokines. Inflammation plays a central role in the development of HCC in MASH, even in the absence of significant fibrosis. The Fibrosis-4 index (FIB-4) should be used as a first-line noninvasive tool to assess fibrosis risk. Additionally, ultrasound-based transient elastography (FibroScan) supports clinicians in assessing steatosis and fibrosis severity. Histologically, MASH is characterized by steatosis, lobular inflammatory changes, and ballooning degeneration of hepatocytes, with or without associated fibrosis. Accurately diagnosing and stratifying MASLD based on fibrosis risk is crucial to identify patients who may benefit from pharmacological treatment or can be managed only with lifestyle interventions. Patients should attain above 10% weight loss through lifestyle modifications. Resmetirom is recommended in F2/F3 fibrosis stages. For treating T2DM, glucagon-like peptide-1 receptor agonists and coagonists, sodium–glucose cotransporter-2 inhibitors, metformin (if glomerular filtration rate exceeds 30 mL/min), and insulin (in decompensated cirrhosis) are preferred. Clinical insights derived from trials are expected to optimize quality of life and long-term outcomes in patients with MASH. Full article

Objectives: Systemic low-grade inflammation is associated with steatohepatitis in adults. We aim to explore if systemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hs-CRP), is also linked to steatotic liver disease in adolescents. Methods: In the cross-sectional Early Vascular Ageing in the YOUth study, systemic low-grade inflammation was measured by hs-CRP and liver fat content was quantified by the controlled attenuation parameters (CAP) derived from FibroScan^® (Echosense, Paris, France) measurements in 14- to 19-year-old Austrian adolescents. Cardiovascular risk factors and anthropometric data were collected through face-to-face interviews, physical examinations, and comprehensive fasting blood analyses. Linear regression models were performed to analyze the association between hs-CRP and CAP values. Results: A total of 1300 adolescents (64.6% female) with a mean age of 17.2 ± 1.3 years were included in this analysis. hs-CRP was significantly associated with CAP values in the simple linear regression model (b = 1.35, p = 0.044) and after adjustment for sex and age (b = 1.84, p = 0.006), suggesting an increase in systemic low-grade inflammation with increasing liver fat content. However, further adjustment for major factors of the metabolic syndrome (Homeostatic Model Assessment for Insulin Resistance, non-high-density lipoprotein cholesterol, body mass index z-score, systolic blood pressure z-score) led to a loss of significance of the mentioned association (b = −0.55, p = 0.419). Conclusions: Systemic low-grade inflammation measured by hs-CRP is linked to higher liver fat content in our adolescent cohort. However, this association is largely driven by components of the metabolic syndrome and the overall metabolic milieu, rather than reflecting liver-specific inflammation. Full article