Non-invasive assessment for alpha-1 antitrypsin deficiencyassociated liver disease: new insights on steatosis and fibrosis in Pi*ZZ carriers

Roohani, Siyer; Tacke, Frank

doi:10.21037/tgh.2019.11.13

Cited by 2 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatic stellate cells (HSCs) are the most important cell type involved in the development and progression of liver fibrosis (6,10). HSCs are activated by inflammatory cytokines and secrete large amounts of collagen protein, leading to excessive deposition of ECM (8). HSCs have become an important therapeutic target for liver fibrosis.…”

Section: Original Articlementioning

confidence: 99%

“…Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) at the injury site, which can lead to liver failure. However, few treatment options are currently available (5)(6)(7)(8) and therefore, the development of new therapeutic drugs for liver fibrosis, along with an understanding of the molecular mechanisms involved, is vitally important. In our previous studies, we found that Sch B mitigated carbon tetrachloride (CCl 4 )-induced liver fibrosis in rats by blocking the transforming growth factor beta (TGF-β)/Smad signaling pathway (9).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ

Chen

Bao

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: Schisandrin B (Sch B), the main ingredient of Schisandra chinensis, displays many bioactivities. This study aimed to identify the drug target of Sch B against liver fibrosis and describe the related molecular mechanisms. Methods:The effects of Sch B on liver fibrosis and macrophage polarization was investigated in vivo and in vitro. Furthermore, we analyzed the regulatory effect of Sch B on peroxisome proliferator-activated receptor gamma (PPARγ).Results: Our data showed that Sch B dramatically alleviated liver inflammation and fibrosis and inhibited macrophage activation via PPARγ. Sch B binds with PPARγ by molecular docking. Immunofluorescence double staining showed that PPARγ was mainly expressed in macrophages rather than hepatic stellate cells (HSCs) in liver fibrosis. Importantly, Sch B strongly inhibited macrophage polarization in fibrotic livers compared with the model group. Further, the results revealed that Sch B efficiently inhibited macrophage polarization and also decreased the levels of inflammatory cytokines in vitro. Knockdown of PPARγ by small interfering RNA (siRNA) inhibited the effect of Sch B on macrophage polarization. Mechanistically, Sch B regulated macrophage polarization through inhibition of the nuclear factor (NF)-κB signaling pathway via PPARγ both in vivo and in vitro.Conclusions: These results suggested that Sch B alleviated carbon tetrachloride (CCl 4 )-induced liver inflammation and fibrosis by inhibiting macrophage polarization via targeting PPARγ.

show abstract

Section: Original Articlementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ

Chen

Bao

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Previous work has identified the particular significance of the PiZZ genotype in the development of early onset emphysema (said to be the cause of 1%-2% of chronic obstructive pulmonary disease (COPD)), 2 as well as liver fibrosis, cirrhosis and hepatocellular carcinoma. 3 Developments in hepatology have included scoring systems for liver disease assessment and monitoring, such as the APRI (aspartate aminotransferase (AST) to platelet ratio) and FIB-4 score (see below). 4 Other key noninvasive liver assessments include ultrasound scans 5 and transient elastography 6 (eg, Fibroscan), the use of which aims to replace or better inform need for invasive investigation with liver biopsy.…”

Section: Introductionmentioning

confidence: 99%

“…Previous work has identified the particular significance of the PiZZ genotype in the development of early onset emphysema (said to be the cause of 1%–2% of chronic obstructive pulmonary disease (COPD)), 2 as well as liver fibrosis, cirrhosis and hepatocellular carcinoma. 3 …”

Section: Introductionmentioning

confidence: 99%

Non-invasive testing for liver pathology in alpha-1 antitrypsin deficiency

et al. 2020

View full text Add to dashboard Cite

BackgroundMany patients with alpha-1 antitrypsin deficiency (A1ATD) receive care in respiratory clinics without access to specialist hepatology expertise. Liver disease can develop asymptomatically, and non-invasive markers of fibrosis may help identify patients who require definitive assessment with liver biopsy. We evaluated the utility of non-invasive markers of liver fibrosis in A1ATD to guide testing in settings without ready access to hepatology expertise.MethodsPatients attending the London A1ATD service undergo assessment using blood tests to calculate the ‘APRI’ and ‘FIB-4’ score, liver ultrasound and Fibroscan. Liver biopsy is offered to patients who have abnormal liver function tests with abnormal liver ultrasound and/or liver stiffness >6 kPa on Fibroscan. Liver biopsies were assessed for the presence of A1AT, steatosis, fibrosis and inflammation.Results75 patients with A1ATD had results for analysis, 56% were female, age 16–82 years. 75% of patients had Fibroscan <6 kPa, 19% had Fibroscan 6–7.9 kPa and 6%>8 kPa. There was a significant correlation between FIB-4 and Fibroscan (r=0.244, p=0.035). Fibroscan >6 kPa corresponded to a FIB-4 score of >1.26. However, FIB-4 >1.26 had poor sensitivity (47%), specificity (32%) and positive-predictive value (PPV; 36%) to identify Fibroscan >6 kPa. The negative-predictive value (NPV) was stronger at 81%. APRI data were similar. Twelve patients underwent liver biopsy, with 11 reports available for analysis. Six had FIB-4 scores<1.26 and five had Fibroscan of <6 kPa. A1AT was present in 64% of biopsies, steatosis in 82%, mild fibrosis in 36%, moderate fibrosis in 9% and severe fibrosis in 9%.ConclusionA combination of liver ultrasound and non-invasive fibrosis tests can help identify patients with A1ATD liver injury. However, APRI and FIB-4 scores alone had poor sensitivity and specificity to justify use as an independent tool for liver pathology in A1ATD.

show abstract

Non-invasive assessment for alpha-1 antitrypsin deficiencyassociated liver disease: new insights on steatosis and fibrosis in Pi*ZZ carriers

Cited by 2 publications

References 21 publications

Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ

Schisandrin B regulates macrophage polarization and alleviates liver fibrosis via activation of PPARγ

Non-invasive testing for liver pathology in alpha-1 antitrypsin deficiency

Contact Info

Product

Resources

About