NAFLD fibrosis score (NFS) can be used in outpatient services to identify chronic vascular complications besides advanced liver fibrosis in type 2 diabetes

Lombardi, Rosa; Airaghi, Lorena; Targher, Giovanni; Serviddio, Gaetano; Maffi, Gabriele; Mantovani, Alessandro; Maffeis, Claudio; Colecchia, Antonio; Villani, Rosanna; Rinaldi, Luca; Orsi, Emanuela; Pisano, Giuseppina; Adinolfi, Luigi Elio

doi:10.1016/j.jdiacomp.2020.107684

Cited by 13 publications

(11 citation statements)

References 12 publications

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“…The literature search identified 2613 papers, after duplication removal. After abstract evaluations, 16 studies were considered for the full text analysis [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] (Figure 1). Three studies have been excluded, since one is a duplication of previously published results [45], and two works did not report the prevalence of neuropathy in NAFLD positive and negative patients [43,44] (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…After abstract evaluations, 16 studies were considered for the full text analysis [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] (Figure 1). Three studies have been excluded, since one is a duplication of previously published results [45], and two works did not report the prevalence of neuropathy in NAFLD positive and negative patients [43,44] (Figure 1). Finally, 13 cross-sectional studies were included.…”

Section: Resultsmentioning

confidence: 99%

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Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Greco

Nascimbeni

Carubbi

et al. 2021

JCM

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Aims. The relationship between nonalcoholic fatty liver disease (NAFLD) and diabetic polyneuropathy (DPN) has been demonstrated in many studies, although results were conflicting. This meta-analysis aims to summarize available data and to estimate the DPN risk among NAFLD patients. Materials and methods. We performed a comprehensive literature review until 4 June 2021. Clinical trials analyzing the association between NAFLD and DPN were included. Results. Thirteen studies (9614 participants) were included. DPN prevalence was significantly higher in patients with NALFD, compared to patients without NAFLD (OR (95%CI) 2.48 (1.42–4.34), p = 0.001; I2 96%). This finding was confirmed in type 2 diabetes (OR (95%CI) 2.51 (1.33–4.74), p = 0.005; I2 97%), but not in type 1 diabetes (OR (95%CI) 2.44 (0.85–6.99), p = 0.100; I2 77%). Also, body mass index and diabetes duration were higher in NAFLD subjects compared to those without NAFLD (p < 0.001), considering both type 2 and type 1 diabetes. Conclusion. Despite a high heterogeneity among studies, a significantly increased DPN prevalence among type 2 diabetes subjects with NAFLD was observed. This result was not found in type 1 diabetes, probably due to the longer duration of disease. Physicians should pay more attention to the early detection of DPN, especially in patients with NAFLD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Greco

Nascimbeni

Carubbi

et al. 2021

JCM

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“…The severity of fibrosis related to steatosis plays an important role in the assessment of CV risk. Non-invasive investigations allow to obtain a reliable and predictive evaluation [ 211 , 212 ].…”

Section: Clinical Impactmentioning

confidence: 99%

Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the “bad company” constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.

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“…Nowadays no pharmacological therapy has been approved for NAFLD, especially in the advanced forms of NASH and fibrosis [ 43 ]. However, since the immune response seems to play a key role in NASH and in its progression to HCC, several trials have explored the possibility to address it to treat patients.…”

Section: Immune-related Therapy In Nafldmentioning

confidence: 99%

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

Lombardi

Piciotti

Dongiovanni

et al. 2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is characterized by an enhanced activation of the immune system, which predispose the evolution to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Resident macrophages and leukocytes exert a key role in the pathogenesis of NAFLD. In particular, CD4+ effector T cells are activated during the early stages of liver inflammation and are followed by the increase of natural killer T cells and of CD8+ T cytotoxic lymphocytes which contribute to auto-aggressive tissue damage. To counteract T cells activation, programmed cell death 1 (PD-1) and its ligand PDL-1 are exposed respectively on lymphocytes and liver cells’ surface and can be targeted for therapy by using specific monoclonal antibodies, such as of Nivolumab, Pembrolizumab, and Atezolizumab. Despite the combination of Atezolizumab and Bevacizumab has been approved for the treatment of advanced HCC, PD-1/PD-L1 blockage treatment has not been approved for NAFLD and adjuvant immunotherapy does not seem to improve survival of patients with early-stage HCC. In this regard, different ongoing phase III trials are testing the efficacy of anti-PD-1/PD-L1 antibodies in HCC patients as first line therapy and in combination with other treatments. However, in the context of NAFLD, immune checkpoints inhibitors may not improve HCC prognosis, even worse leading to an increase of CD8+PD-1+ T cells and effector cytokines which aggravate liver damage. Here, we will describe the main pathogenetic mechanisms which characterize the immune system involvement in NAFLD discussing advantages and obstacles of anti PD-1/PDL-1 immunotherapy.

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NAFLD fibrosis score (NFS) can be used in outpatient services to identify chronic vascular complications besides advanced liver fibrosis in type 2 diabetes

Cited by 13 publications

References 12 publications

Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis

Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

PD-1/PD-L1 Immuno-Mediated Therapy in NAFLD: Advantages and Obstacles in the Treatment of Advanced Disease

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