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Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) and Concomitant Illnesses: Diagnostic and Therapeutic Implications

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: 5 November 2026 | Viewed by 3481

Special Issue Editors

Dr. Kamran Qureshi

E-Mail Website
Guest Editor
Gastroenterology & Hepatology, Saint Louis University, St. Louis, MO, USA
Interests: liver diseases; drug-induced liver injury; hepatology; metabolic syndrome
Dr. Lewis Frey

E-Mail Website
Guest Editor
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Saint Louis University, Saint Louis, MO 63103, USA
Interests: accuracy; acute liver failure; liver diseases; relevance; retrieval augmented generation

Special Issue Information

Dear Colleagues,

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) represents a comprehensive category of liver diseases that are closely linked to metabolic dysfunction, such as insulin resistance, obesity, and dyslipidemia. MASLD encompasses a range of conditions, including steatotic liver disease and Metabolic Dysfunction-Associatedsteatohepatitis (MASH), which can progress to severe liver complications like cirrhosis and hepatocellular carcinoma. The rising prevalence of MASLD correlates with increasing rates of metabolic syndrome and is now recognized as a significant public health concern. The change in definition has allowed MASLD to be considered as an inclusive liver disease and can be present along with other forms of chronic liver diseases. This Special Issue focuses on the evolving understanding of overlap of MASLD, with other chronic liver diseases to understand its impact on natural history of individual diseases.

In addition, we delve into the challenges and opportunities in diagnosing MASLD, emphasizing novel biomarkers, non-invasive diagnostic tools, and emerging therapeutic approaches along with concomitant chronic liver diseases. With a focus on early intervention, lifestyle modifications, and the future directions in MASLD research, this issue aims to enhance clinical management and treatment strategies in such scenarios of overlapping liver conditions.

Dr. Kamran Qureshi
Dr. Lewis Frey
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • metabolic dysfunction-associated steatotic liver disease (MASLD)
  • metabolic dysfunction-associated steatohepatitis (MASH)
  • chronic liver diseases
  • metabolic syndrome
  • viral hepatitis
  • autoimmune liver diseases

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Published Papers (3 papers)

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14 pages, 1178 KB  
Article
Alcohol Intake, Cardiometabolic Risk, Fibrosis, and Gut Microbiota in Steatotic Liver Disease: A Population-Based Health Checkup Study
by Keisuke Furusawa, Chikara Iino, Keita Mikami, Satoshi Sato, Kenta Yoshida, Shigeyuki Nakaji, Tatsuya Mikami and Hirotake Sakuraba
J. Clin. Med. 2026, 15(8), 2860; https://doi.org/10.3390/jcm15082860 - 9 Apr 2026
Viewed by 423
Abstract
Background: The real-world risk profiles of newly defined steatotic liver disease (SLD) subtypes—MASLD, MetALD, and ALD—remain incompletely described in community settings. Methods: A cross-sectional analysis of 950 health-checkup participants was conducted. SLD (CAP ≥ 248 dB/m) and significant fibrosis (LSM ≥ [...] Read more.
Background: The real-world risk profiles of newly defined steatotic liver disease (SLD) subtypes—MASLD, MetALD, and ALD—remain incompletely described in community settings. Methods: A cross-sectional analysis of 950 health-checkup participants was conducted. SLD (CAP ≥ 248 dB/m) and significant fibrosis (LSM ≥ 7.0 kPa) were evaluated by transient elastography. Associations between alcohol intake, cardiometabolic factors, fibrosis, and gut microbiota (16S rRNA sequencing) were assessed. Results: Among 950 participants, 310 (33%) had SLD (MASLD, n = 222; MetALD, n = 41; ALD, n = 23). Treated as a continuous exposure, higher alcohol intake was significantly correlated with elevated systolic/diastolic blood pressure, triglycerides, AST, and γ-GTP, but inversely correlated with HOMA-IR (all p < 0.05). In multivariable logistic regression adjusting for cardiometabolic factors, BMI was the only independent predictor of fibrosis (adjusted OR 1.22, 95% CI 1.11–1.35, p < 0.01), whereas alcohol intake showed no independent association. Furthermore, microbiota analysis revealed that ALD-related SLD was characterized by significant depletion of Blautia and enrichment of Gemella (FDR q < 0.05) compared to non-SLD controls, indicating an alcohol-associated dysbiosis signature. Conclusions: In early-stage SLD, alcohol intake continuously exacerbates cardiometabolic risk factors, whereas fibrosis is predominantly driven by BMI. These findings support quantitative alcohol/BMI integration for risk stratification, alongside microbiota profiling to detect ALD-related dysbiosis. Full article
(This article belongs to the Special Issue Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) and Concomitant Illnesses: Diagnostic and Therapeutic Implications)
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18 pages, 912 KB  
Article
Rising Cardiometabolic Comorbidity and Inpatient Resource Utilization Among Hospitalized Patients with Hepatocellular Carcinoma, 2018–2022
by Muhammad Haris Latif, Ayesha Kang, Eman Mazhar, Kahee Amedi, Joel Riley, Hani-El Halawany and Kamran Qureshi
J. Clin. Med. 2026, 15(6), 2386; https://doi.org/10.3390/jcm15062386 - 20 Mar 2026
Viewed by 1475
Abstract
Background: Hospitalizations for hepatocellular carcinoma (HCC) increasingly reflect a complex interplay among chronic liver disease, cardiometabolic comorbidities, and systemic complications, which now exert greater influence on patient outcomes than tumor-specific factors alone. Despite this shift, contemporary data regarding the impact of the [...] Read more.
Background: Hospitalizations for hepatocellular carcinoma (HCC) increasingly reflect a complex interplay among chronic liver disease, cardiometabolic comorbidities, and systemic complications, which now exert greater influence on patient outcomes than tumor-specific factors alone. Despite this shift, contemporary data regarding the impact of the evolving comorbidity burden on inpatient resource utilization and procedural care remain limited. This study examines national trends in inpatient characteristics, procedural utilization, and outcomes among patients hospitalized with HCC between 2018 and 2022. Methods: A retrospective, cross-sectional analysis of adult hospitalizations was performed using the National Inpatient Sample (NIS) from 2018 to 2022. Hospitalizations involving HCC were identified through ICD-10 diagnosis codes, encompassing both principal and secondary diagnoses. Survey-weighted analyses were used to estimate national prevalence, in-hospital mortality, length of stay (LOS), and total hospital charges. Temporal trends were evaluated using survey-weighted logistic or linear regression, with calendar year as a continuous variable. Multivariable survey-weighted logistic regression models were constructed to identify adjusted predictors of inpatient mortality and procedural utilization, including liver transplantation, hepatic resection, and transjugular intrahepatic portosystemic shunt (TIPS) placement. Results: During the study period, an estimated 275,000 HCC-related hospitalizations occurred nationwide. The prevalence of cardiometabolic comorbidities increased significantly over time (all p < 0.001), including MASLD (6.6% to 8.7%), obesity (10.6% to 13.7%), diabetes (36.0% to 38.9%), and dyslipidemia (26.4% to 34.4%). In-hospital mortality rose from 8.82% (95% CI, 8.40–9.24%) in 2018 to 9.23% (95% CI, 8.81–9.65%) in 2022, with the highest rate in 2020 (9.42%). In parallel, inpatient resource utilization rose, as reflected by longer lengths of stay and higher hospitalization charges. Utilization of diagnostic endoscopic procedures, such as esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography, increased, whereas rates of definitive inpatient oncologic and portal hypertension-directed interventions—including liver transplantation, hepatic resection, and TIPS—remained low and stable. In-hospital mortality was independently associated with markers of hepatic decompensation and systemic illness, including hepatic encephalopathy, acute kidney injury, sepsis, and hepatorenal syndrome. These associations were stronger than those observed for tumor-directed procedures, as reflected by inpatient procedural utilization patterns. Conclusions: Between 2018 and 2022, inpatient resource utilization among patients hospitalized with hepatocellular carcinoma increased in parallel with rising cardiometabolic comorbidity. It was primarily driven by management of hepatic decompensation and systemic illness rather than oncologic intervention. These findings characterize the evolving complexity of HCC hospitalizations in the contemporary inpatient setting. Full article
(This article belongs to the Special Issue Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) and Concomitant Illnesses: Diagnostic and Therapeutic Implications)
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20 pages, 1462 KB  
Systematic Review
Primary, Secondary and Exploratory Endpoints in Phase 2 and 3 Clinical Trials with Novel Therapies in MASH Cirrhosis: A Systematic Review
by Grzegorz Żurakowski, Anna Wiela-Hojeńska and Paweł Petryszyn
J. Clin. Med. 2026, 15(7), 2621; https://doi.org/10.3390/jcm15072621 - 30 Mar 2026
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Abstract
Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease and a major driver of cirrhosis, liver failure, and mortality worldwide. Despite the urgent need for effective therapies, clinical trials in MASH cirrhosis face substantial challenges due to the heterogeneity and the lack [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease and a major driver of cirrhosis, liver failure, and mortality worldwide. Despite the urgent need for effective therapies, clinical trials in MASH cirrhosis face substantial challenges due to the heterogeneity and the lack of standardization in study endpoints. A clear understanding of how endpoints are defined and applied across trials is critical for interpreting efficacy, comparing results, and guiding regulatory decisions. The objective of this systematic review was to classify and critically evaluate the primary, secondary, and exploratory endpoints used in phase 2 and 3 clinical trials of novel therapies for MASH cirrhosis, and to assess their consistency, strengths, and limitations. Methods: PubMed, Embase, and Cochrane Library databases were searched to identify Phase 2 and 3 trials of novel therapies for MASH-related cirrhosis. Studies of adults with biopsy-confirmed MASH cirrhosis in which clinical, histological, hemodynamic, imaging, and laboratory outcomes being assessed were included. Results: Nine eligible trials were included. Histological measures, most commonly improvement in fibrosis stage without worsening of MASH, were generally considered key efficacy outcomes. Biochemical (e.g., ALT, AST, Pro-C3, composite fibrosis scores) and imaging-based markers (e.g., liver stiffness) were widely used as secondary or exploratory endpoints and more frequently demonstrated treatment-related changes than histology. Hepatic venous pressure gradient (HVPG) was selected as a primary endpoint in some studies and as an exploratory outcome in others. Patient-centered outcomes, when incorporated, were typically exploratory. Conclusions: Phase 2 and 3 trials in MASH cirrhosis employ diverse and inconsistently defined endpoints, with limited standardization across studies. Establishing consensus on endpoint classification, definitions and clinical relevance is critical to advancing therapeutic development and ensuring regulatory acceptance in this high-risk patient population. Full article
(This article belongs to the Special Issue Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) and Concomitant Illnesses: Diagnostic and Therapeutic Implications)
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