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Recent Clinical Research on Nonalcoholic Fatty Liver Disease
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Recent Clinical Research on Nonalcoholic Fatty Liver Disease

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: closed (25 August 2024) | Viewed by 10211

Special Issue Editor

Dr. Gerond V. Lake-Bakaar

E-Mail Website
Guest Editor
Transplant Center, Presbyterian Saint Luke's Medical Center, Denver, CO 80218, USA
Interests: hepatitis; liver cirrhosis; alcoholic liver disease; liver failure; nonalcoholic steatohepatitis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The last decade saw enormous progress in our ability to treat and control chronic hepatitis C virus liver disease. In more recent years, nonalcoholic fatty liver disease (NAFLD) has emerged as a significant cause of liver disease, affecting millions worldwide. This chronic condition is characterized by the build-up of fat in the liver, which can lead to inflammation, fibrosis, and even cirrhosis. While the traditional risk factors for liver disease, such as hepatitis C, have declined due to effective treatment and prevention measures, NAFLD has become more prevalent due to changes in lifestyle and diet.

In this Special Issue, we welcome authors to submit papers on the global changes in disease prevalence. Clinical advances in the diagnoses; factors associated with disease progression; and the results of ongoing trials and advances in disease treatment are encouraged.

Dr. Gerond V. Lake-Bakaar
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

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

  • NAFLD
  • NASH
  • cirrhosis
  • hepatocellular carcinoma

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Published Papers (7 papers)

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Research

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17 pages, 4729 KiB  
Article
Impact of Non-Alcoholic Fatty Liver Disease on Sepsis Inpatient Outcomes: A Nationwide Sample Analysis (2000–2019)
by Xiuhong Lyu, Bolun Liu, Yiting Li, Yichen Wang, John Miskovsky, Melissa Gaitanis, Kittichai Promrat and Wen-Chih Wu
J. Clin. Med. 2024, 13(19), 5737; https://doi.org/10.3390/jcm13195737 - 26 Sep 2024
Viewed by 1023
Abstract
Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This [...] Read more.
Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD’s impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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16 pages, 575 KiB  
Article
Retrospective Longitudinal Observational Study on the Long-Term Effects of Sodium-Glucose Cotransporter-2 Inhibitors on the Development of Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetic Japanese Patients
by Hisayuki Katsuyama, Seiichi Horinaka, Mariko Hakoshima, Hiroki Adachi and Hidekatsu Yanai
J. Clin. Med. 2024, 13(16), 4929; https://doi.org/10.3390/jcm13164929 - 21 Aug 2024
Cited by 1 | Viewed by 904
Abstract
Background/Objectives: The health burden of metabolic dysfunction-associated fatty liver disease (MASLD) has been increasing lately. Cardiovascular disease (CVD) is the main cause of death in MASLD patients; therefore, the treatments for MASLD should improve both CV risk factors such as obesity, diabetes, [...] Read more.
Background/Objectives: The health burden of metabolic dysfunction-associated fatty liver disease (MASLD) has been increasing lately. Cardiovascular disease (CVD) is the main cause of death in MASLD patients; therefore, the treatments for MASLD should improve both CV risk factors such as obesity, diabetes, and dyslipidemia, in addition to an improvement in liver function. The evidence on the long-term effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on the progression of MASLD in Asian populations is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at our institute. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between 1 April 2014 and 31 March 2018. We collected the data on metabolic parameters, including laboratory data and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. Three-year SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein cholesterol, triglyceride, and non-high-density lipoprotein cholesterol (non-HDL-C). Such favorable changes in serum lipids were remarkable in patients with statins. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, long-term SGLT2is treatment may be an ideal therapy for MASLD patients. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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13 pages, 870 KiB  
Article
Effects of Combined Low-Dose Spironolactone Plus Vitamin E versus Vitamin E Monotherapy on Lipidomic Profile in Non-Alcoholic Fatty Liver Disease: A Post Hoc Analysis of a Randomized Controlled Trial
by Anastasios Semertzidis, Thomai Mouskeftara, Helen Gika, Petros Pousinis, Kali Makedou, Antonis Goulas, Jannis Kountouras and Stergios A. Polyzos
J. Clin. Med. 2024, 13(13), 3798; https://doi.org/10.3390/jcm13133798 - 28 Jun 2024
Cited by 1 | Viewed by 1475
Abstract
Background/Objectives: Lipid dysmetabolism seems to contribute to the development and progression of nonalcoholic fatty liver disease (NAFLD). Our aim was to compare serum lipidomic profile between patients with NAFLD having received monotherapy with vitamin E (400 IU/d) and those having received combination [...] Read more.
Background/Objectives: Lipid dysmetabolism seems to contribute to the development and progression of nonalcoholic fatty liver disease (NAFLD). Our aim was to compare serum lipidomic profile between patients with NAFLD having received monotherapy with vitamin E (400 IU/d) and those having received combination therapy with vitamin E (400 IU/d) and low-dose spironolactone (25 mg/d) for 52 weeks. Methods: This was a post hoc study of a randomized controlled trial (NCT01147523). Serum lipidomic analysis was performed in vitamin E monotherapy group (n = 15) and spironolactone plus vitamin E combination therapy group (n = 12). We employed an untargeted liquid chromatography–mass spectrometry lipid profiling approach in positive and negative ionization mode. Results: Univariate analysis revealed 36 lipid molecules statistically different between groups in positive mode and seven molecules in negative mode. Multivariate analysis in negative mode identified six lipid molecules that remained robustly different between groups. After adjustment for potential confounders, including gender, omega-3 supplementation, leptin concentration and homeostasis model assessment—insulin resistance (HOMA-IR), four lipid molecules remained significant between groups: FA 20:5, SM 34:2;O2, SM 42:3;O2 and CE 22:6, all being higher in the combination treatment group. Conclusions: The combination of spironolactone with vitamin E led to higher circulating levels of four lipid molecules than vitamin E monotherapy, after adjustment for potential confounders. Owing to very limited relevant data, we could not support that these changes in lipid molecules may be beneficial or not for the progression of NAFLD. Thus, mechanistic studies are warranted to clarify the potential clinical significance of these findings. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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9 pages, 685 KiB  
Article
Prevalence of Steatotic Liver Disease Based on a New Nomenclature in the Japanese Population: A Health Checkup-Based Cross-Sectional Study
by Takao Miwa, Satoko Tajirika, Nanako Imamura, Miho Adachi, Ryo Horita, Tatsunori Hanai, Taku Fukao, Masahito Shimizu and Mayumi Yamamoto
J. Clin. Med. 2024, 13(4), 1158; https://doi.org/10.3390/jcm13041158 - 19 Feb 2024
Cited by 5 | Viewed by 1714
Abstract
This cross-sectional study examined the prevalence and characteristics of steatotic liver disease (SLD) based on a recently introduced nomenclature in the Japanese health checkup population. SLD was evaluated using liver ultrasonography, and participants were categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic [...] Read more.
This cross-sectional study examined the prevalence and characteristics of steatotic liver disease (SLD) based on a recently introduced nomenclature in the Japanese health checkup population. SLD was evaluated using liver ultrasonography, and participants were categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol associated steatotic liver disease (MetALD), alcohol-associated/related liver disease (ALD), and cryptogenic SLD groups. The prevalence and characteristics of the SLD subclasses were assessed, and subgroup analyses were conducted for the non-obese (body mass index [BMI] ≤ 25 kg/m2) and lean (BMI ≤ 23 kg/m2) populations. Among the 694 participants, with a median age of 47 years and comprising 54% males, the prevalence of MASLD, MetALD, ALD, and cryptogenic SLD was 26%, 2%, 1%, and 2%, respectively. A remarkable difference was observed in the prevalence of SLD subclasses according to age, sex, and BMI. Subgroup analyses revealed heterogeneous demographic, clinical, and biochemical parameters between the SLD categories. Individuals with MetALD had higher gamma-glutamyl transferase levels, lower platelet counts, and higher fibrosis-4 index than did those with MASLD. Furthermore, the prevalence of non-obese and lean MASLD was 13% and 6%, respectively. This study provides preliminary information on the prevalence of SLD based on a new nomenclature in the Japanese population. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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12 pages, 911 KiB  
Article
Prevalence and Risk Factors of MASLD and Liver Fibrosis amongst the Penitentiary Population in Catalonia: The PRISONAFLD Study
by Jesús Rivera-Esteban, Alba Jiménez-Masip, Sergio Muñoz-Martínez, Salvador Augustin, Rafael A. Guerrero, Pablo Gabriel-Medina, Roser Ferrer-Costa, Francisco Rodríguez-Frías, Elisabet Turu, Andrés Marco, Juan M. Pericàs and on behalf of the PRISONAFLD Study Group Collaborators
J. Clin. Med. 2023, 12(23), 7276; https://doi.org/10.3390/jcm12237276 - 24 Nov 2023
Cited by 4 | Viewed by 1728
Abstract
Background and Aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence [...] Read more.
Background and Aims: The prevalence of chronic non-communicable diseases, particularly metabolic syndrome (MetS), has increased among the prison population. Nevertheless, we have limited data on metabolic dysfunction-associated steatotic liver disease (MASLD), the hepatic manifestation of this syndrome. We aimed to investigate the prevalence and risk factors of MASLD and MASLD-associated liver fibrosis in the penitentiary population in Catalonia, Spain. Method: A cross-sectional observational study involving eight penitentiary centers. Participants had at least one metabolic disorder and were at a closed-regimen penitentiary. Individuals with concomitant liver diseases and/or alcohol risk consumption were excluded. Significant fibrosis and MASLD were defined as liver stiffness ≥8 kPa and a controlled attenuation parameter ≥275 dB/m by vibration-controlled transient elastography (VCTE), respectively. After exclusions, metabolic inmates with VCTE were analyzed. Logistic regression analysis was performed to identify predictors of MASLD and MASLD-associated significant fibrosis. Results: Out of the 4338 inmates studied, 1290 (29.7%) had metabolic disorders, and 646 (14.9%) underwent VCTE. The mean age was 48.0 years (SD 12.1), and 89.5% were male. MASLD prevalence was 33.9%. Significant fibrosis and MASLD-associated significant fibrosis were found in 16.4% and 9.4% of inmates, respectively. In the multivariate analysis, T2D, waist circumference, MetS, and higher ALT values were identified as independent risk factors for MASLD and MASLD-associated significant fibrosis amongst the prison population. Conclusions: Metabolic disorders including MASLD are highly prevalent among inmates. The prevalence of significant fibrosis seems notably higher than that of the general population, underscoring the need for targeted screening programs and therapeutic interventions in the incarcerated population. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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21 pages, 1741 KiB  
Article
Hepatic Involvement across the Metabolic Syndrome Spectrum: Non-Invasive Assessment and Risk Prediction Using Machine Learning
by Adelaida Solomon, Călin Remus Cipăian, Mihai Octavian Negrea, Adrian Boicean, Romeo Mihaila, Corina Beca, Mirela Livia Popa, Sebastian Mihai Grama, Minodora Teodoru and Bogdan Neamtu
J. Clin. Med. 2023, 12(17), 5657; https://doi.org/10.3390/jcm12175657 - 30 Aug 2023
Cited by 4 | Viewed by 1686
Abstract
Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. [...] Read more.
Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. Liver fibrosis is the main predictor of liver-related morbidity and mortality. Non-invasive tests (NIT) such as the Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), hepatic steatosis index (HIS), transient elastography (TE), and combined scores (AGILE3+, AGILE4) facilitate the detection of liver fibrosis or steatosis. Our study enrolled 217 patients with suspected MASLD, 109 of whom were diagnosed with MetS. We implemented clinical and biological evaluations complemented by transient elastography (TE) to discern the most robust predictors for liver disease manifestation patterns. Patients with MetS had significantly higher values of FIB4, APRI, HSI, liver stiffness, and steatosis parameters measured by TE, as well as AGILE3+ and AGILE4 scores. Machine-learning algorithms enhanced our evaluation. A two-step cluster algorithm yielded three clusters with reliable model quality. Cluster 1 contained patients without significant fibrosis or steatosis, while clusters 2 and 3 showed a higher prevalence of significant liver fibrosis or at least moderate steatosis as measured by TE. A decision tree algorithm identified age, BMI, liver enzyme levels, and metabolic syndrome characteristics as significant factors in predicting cluster membership with an overall accuracy of 89.4%. Combining NITs improves the accuracy of detecting patterns of liver involvement in patients with suspected MASLD. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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Review

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12 pages, 465 KiB  
Review
MASLD-Related Hepatocarcinoma: Special Features and Challenges
by Carmen Yagüe-Caballero, Diego Casas-Deza, Andrea Pascual-Oliver, Silvia Espina-Cadena, Jose M. Arbones-Mainar and Vanesa Bernal-Monterde
J. Clin. Med. 2024, 13(16), 4657; https://doi.org/10.3390/jcm13164657 - 8 Aug 2024
Viewed by 985
Abstract
Metabolic-associated steatohepatitis liver disease (MASLD) currently impacts a quarter of the global population, and its incidence is expected to increase in the future. As a result, hepatocellular carcinoma associated with MASLD is also on the rise. Notably, this carcinoma does not always develop [...] Read more.
Metabolic-associated steatohepatitis liver disease (MASLD) currently impacts a quarter of the global population, and its incidence is expected to increase in the future. As a result, hepatocellular carcinoma associated with MASLD is also on the rise. Notably, this carcinoma does not always develop alongside liver cirrhosis, often leading to a more advanced stage at diagnosis. The challenge lies in accurately identifying patients who are at a higher risk to tailor screening processes effectively. Additionally, several therapeutic approaches are being explored to prevent hepatocellular carcinoma, although there are no universally accepted guidelines yet. Full article
(This article belongs to the Special Issue Recent Clinical Research on Nonalcoholic Fatty Liver Disease)
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