The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Yu, Ming‐Lung; Fang, Tzu-Jung; Hung, Wei‐Wen; Tsai, Hung-Chin; Tsai, Yi‐Chun

doi:10.3390/biomedicines10071487

Cited by 11 publications

(4 citation statements)

References 55 publications

(70 reference statements)

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“…After the onset of menopause, the incidence is comparable. The same higher incidence for the male gender, but lower compared to our study (51.8%), was present in a Chinese study that investigated the factors of progression to fibrosis in patients with NAFLD and T2DM [35]. Regarding the mean age of the patients, it was higher in patients with HS and T2DM compared to the group of patients with NASH and T2DM.…”

Section: Discussionsupporting

confidence: 77%

A Current Approach to Non-Alcoholic Steatohepatitis in Type 2 Diabetes Mellitus Patients

Stan,

Biciusca,

Biciusca

et al. 2023

Gastroenterology Insights

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(1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease into non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with hepatic steatosis (HS) and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers, serum ferritin (SF) and the neutrophil-percentage-to-albumin ratio (NPAR) showed higher and statistically significant mean values (p = 0.003 respectively p = 0.03) in the group of patients with NASH and T2DM. Conclusions: Consequently, it is essential to identify alternative markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures (LBP) and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

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Section: Discussionsupporting

confidence: 77%

A Current Approach to Non-Alcoholic Steatohepatitis in Type 2 Diabetes Mellitus Patients

Stan,

Biciusca,

Biciusca

et al. 2023

Gastroenterology Insights

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“… 11–13 Higher levels of liver enzymes are independently associated with LF. 14–16 Other risk factors include age, 17 , 18 dyslipidemia, 19 hypertension 20 and race. 11 , 21 To date, there are few studies to explore the relevant factors of LF in Chinese diabetes patients combined with NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Luo

Wang

Zhang

et al. 2023

IJGM

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Purpose Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are frequently co-occurring diseases. Liver fibrosis (LF), with increasing incidence, has a prognostic value for NAFLD mortality. Our study aimed to investigate the relevant factors for FL in T2DM individuals with NAFLD. Patients and Methods A total of 565 T2DM patients with NAFLD from Hebei General Hospital participated in the study. Patients underwent an abdominal ultrasound, a questionnaire and laboratory tests. The fibrosis-4 index (FIB-4) was used to evaluate LF, with FIB ≥1.3 indicating LF and FIB ≥2.67 indicating F3-4 fibrosis. Results Compared with NLF group, LF group had higher levels of systolic blood pressure (SBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (GGT). The glomerular filtration rate (GFR), low-density lipoprotein cholesterol (LDL), glycated hemoglobin (HbA1c), and platelets (PLT) in LF patients were lower than those without LF. Patients with LF were older than those without LF. ALT, AST, and GGT in patients with severe LF were higher than those with mild LF, while platelet was lower. Age, SBP, duration of diabetes, ALT, AST, and GGT were positively correlated with FIB-4, while eGFR, TC, LDL, and HbA1c were negatively correlated with FIB-4. Logistic regression showed that age, SBP, ALT, GGT, LDL, and PLT were independently associated with LF. Conclusion For T2DM patients combined with NAFLD, older age, higher SBP, higher ALT, higher GGT, lower LDL, and lower PLT were relevant factors for LF.

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“…Accumulating studies have confirmed that one of the key risk factors for the development of liver fibrosis is liver aging, so we also established a transcriptomic signature that could be used to assess the degree of liver aging [28][29][30]. To construct a liver aging-related transcriptomic signature (Liver aging signature), we included 4 transcriptomic datasets comparing the livers of older individuals with younger individuals by searching the GEO database, including GSE61260, GSE107037, GSE133815 and GSE183915.…”

Section: Establishment and Validation Of Key Transcriptomic Signaturesmentioning

confidence: 99%

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages

Huang

Shi

et al. 2023

J Transl Med

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Background There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. Methods To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. Results The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-β signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. Conclusion Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

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The Determinants of Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

Cited by 11 publications

References 55 publications

A Current Approach to Non-Alcoholic Steatohepatitis in Type 2 Diabetes Mellitus Patients

A Current Approach to Non-Alcoholic Steatohepatitis in Type 2 Diabetes Mellitus Patients

Factors Associated with Liver Fibrosis in Chinese Patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages

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