Association between lower plasma adiponectin levels and higher liver stiffness in type 2 diabetic individuals with nonalcoholic fatty liver disease: an observational cross-sectional study

Mantovani, Alessandro; Zusi, Chiara; Csermely, Alessandro; Salvagno, Gian Luca; Colecchia, Antonio; Lippi, Giuseppe; Maffeis, Claudio; Targher, Giovanni

doi:10.1007/s42000-022-00387-6

Cited by 10 publications

(10 citation statements)

References 45 publications

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“…Mikolasevic et al 26 found that HOMA-IR was independently associated with hepatic steatosis, but not with moderate and advanced LF in T2DM patients with NAFLD. Mantovani et al 55 conducted a cross-sectional study on T2DM patients who were not treated with insulin. The diagnosis of NAFLD is based on abdominal color ultrasound and liver hardness measurement.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…In conclusion, the Agile 3+ score has been demonstrated to perform satisfactorily in the noninvasive One benefit of this approach is identifying patients who would benefit the most from preventive strategies focused on managing comorbidities and weight loss. [18,29,30] This can help prevent the progression of MASLD to advanced liver disease. Additionally, accurately excluding patients without advanced fibrosis is crucial as it allows a better allocation of health and economic resources in tertiary care centers.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis

Dalbeni,

Lombardi,

Henrique

et al. 2023

Hepatology

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Background and Aims: A simple non-invasive score, the Agile3+ score, combining liver stiffness measurement (LSM), aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for identification of advanced fibrosis in patients with suspected non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease (MASLD), so currently, the two terms are interchangeable. Methods: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the 24th of April 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤0.451) and rule-in (≥0.679) cut-offs. Results: We included 6 observational studies (total 6955 participants) with biopsy-proven NAFLD (mean age 53 [SE 4] years, mean BMI 30.9 [SE 2.3] Kg/m2, 54.0% men, prevalence of diabetes 59.6%). The pooled prevalence of advanced fibrosis (≥F3) was 42.1%. By the rule-out cut-off, the overall sensitivity and specificity were 88% (95%CI 81-93%; I2=89.2%) and 65% (95%CI 54-75%; I2=97.6%), respectively. By the rule-in cut-off, the overall sensitivity and specificity were 68% (95%CI 57-78%; I2=91.1%) and 87% (95%CI 80-92%; I2=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p<0.01), BMI (p<0.01), and, although not statistically significant, sex (p=0.06). Conclusion: Our systematic review and meta-analysis suggest that Agile3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

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“…46 Adiponectin is specifically expressed in adipose tissue and its serum level is inversely associated with the risk of type 2 diabetes and the presence of fibrosis in NAFLD. 47,48 Adiponectin inhibits progression to steatosis/steatohepatitis 49 A recent study from a single referral hospital in Japan reported that 105 out of 535 (20%) exhibited at least partial SH-HCC feature and more prevalent SH-HCC (40%) was observed among patients with NASH compared with those with other etiologies. 53 Other histological studies from the United States and Brazil showed that 71% and 70% of HCC from NAFLD were diagnosed as SH-HCC, respectively.…”

Section: Fib Ros Is -Independenthepat O C a Rci Nog Ene S Is From Nafldmentioning

confidence: 99%

“…For instance, adipokines released from adipose tissue can influence hepatocarcinogenesis from NAFLD 46 . Adiponectin is specifically expressed in adipose tissue and its serum level is inversely associated with the risk of type 2 diabetes and the presence of fibrosis in NAFLD 47,48 . Adiponectin inhibits progression to steatosis/steatohepatitis 49 and protects against liver hepatocarcinogenesis by inducing apoptosis via increased phosphorylation of JNK and activation of caspase 3 50 .…”

Section: Fibrosis‐independent Hepatocarcinogenesis From Nafldmentioning

confidence: 99%

Clinico‐histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease

Fujiwara,

Nakagawa

2023

Cancer Science

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Patients with nonalcoholic fatty liver disease (NAFLD) continue to increase with the epidemics of obesity, and NAFLD is estimated to become the most prevalent etiology of hepatocellular carcinoma (HCC). Recently, NAFLD‐HCC has been recognized to have clinico‐histologically and molecularly distinct features from those from other etiologies, including a lower incidence rate of HCC and less therapeutic efficacy to immune checkpoint inhibitors (ICIs). Consistent with the clinical observations that up to 50% of NAFLD‐HCC occurs in the absence of cirrhosis, the imbalance of pro‐ and antitumorigenic hepatic stellate cells termed as myHSC and cyHSC can contribute to the creation of an HCC‐prone hepatic environment, independent of the absolute fibrosis abundance. Immune deregulations by accumulated metabolites in NAFLD‐affected livers, such as a fatty‐acid‐induced loss of cytotoxic CD4 T cells serving for immune surveillance and “auto‐aggressive” CXCR6+ CD8 T cells, may promote hepatocarcinogenesis and diminish therapeutic response to ICIs. Steatohepatitic HCC (SH‐HCC), characterized by the presence of fat accumulation in tumor cells, ballooned tumor cells, Mallory–Denk body, interstitial fibrosis, and intratumor immune cell infiltration, may represent a metabolic reprogramming for adapting to a lipid‐rich tumor microenvironment by downregulating CPT2 and leveraging its intermediates as an “oncometabolite.” Genome‐wide analyses suggested that SH‐HCC may be more responsive to ICIs given its mutual exclusiveness with β‐catenin mutation/activation that promotes immune evasion. Thus, further understanding of NAFLD‐specific hepatocarcinogenesis and HCC would enable us to improve the current daily practice and eventually the prognoses of patients with NAFLD.

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Association between lower plasma adiponectin levels and higher liver stiffness in type 2 diabetic individuals with nonalcoholic fatty liver disease: an observational cross-sectional study

Cited by 10 publications

References 45 publications

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

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

Diagnostic accuracy of AGILE 3+ score for advanced fibrosis in patients with NAFLD: A systematic review and meta-analysis

Clinico‐histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease

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