Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is ...a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA).
A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics.
Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36-2.79, I
=76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52-3.24, I
=67%) and 1.55 (95%CI: 1.03-2.33, I
=69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41-2.75, I
=71%), 2.09 (95%CI, 1.49-2.91, I
=42%) and 2.05 (95%CI, 1.59-2.64, I
=0%) for all CCAs, iCCA, and eCCA, respectively.
This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted.
The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).
Liver fibrosis is characterized by the activation and migration of hepatic stellate cells (HSCs), followed by matrix deposition. Recently, several studies have shown the importance of extracellular ...vesicles (EVs) derived from liver cells, such as hepatocytes and endothelial cells, in liver pathobiology. While most of the studies describe how liver cells modulate HSC behavior, an important gap exists in the understanding of HSC‐derived signals and more specifically HSC‐derived EVs in liver fibrosis. Here, we investigated the molecules released through HSC‐derived EVs, the mechanism of their release, and the role of these EVs in fibrosis. Mass spectrometric analysis showed that platelet‐derived growth factor (PDGF) receptor‐alpha (PDGFRα) was enriched in EVs derived from PDGF‐BB‐treated HSCs. Moreover, patients with liver fibrosis had increased PDGFRα levels in serum EVs compared to healthy individuals. Mechanistically, in vitro tyrosine720‐to‐phenylalanine mutation on the PDGFRα sequence abolished enrichment of PDGFRα in EVs and redirected the receptor toward degradation. Congruently, the inhibition of Src homology 2 domain tyrosine phosphatase 2, the regulatory binding partner of phosphorylated tyrosine720, also inhibited PDGFRα enrichment in EVs. EVs derived from PDGFRα‐overexpressing cells promoted in vitro HSC migration and in vivo liver fibrosis. Finally, administration of Src homology 2 domain tyrosine phosphatase 2inhibitor, SHP099, to carbon tetrachloride–administered mice inhibited PDGFRα enrichment in serum EVs and reduced liver fibrosis. Conclusion: PDGFRα is enriched in EVs derived from PDGF‐BB‐treated HSCs in an Src homology 2 domain tyrosine phosphatase 2–dependent manner and these PDGFRα‐enriched EVs participate in development of liver fibrosis. (Hepatology 2018;68:333‐348).
Background
Laparoscopic sleeve gastrectomy (LSG) is a commonly performed bariatric surgery. Studies have suggested that LSG can provide effective and sustainable weight loss although most of them ...were conducted in Western populations. Our aim was to characterize the midterm outcome of LSG in Asians with obesity.
Methods
MEDLINE and EMBASE were searched through August 2019 for studies that reported % total body weight loss (TBWL) and/or % excess weight loss (EWL) at 3 and/or 5 years among adult Asians with obesity who underwent LSG. Data on complications and surgical revision rate were also extracted. The pooled effect size and 95% confidence interval (CI) were calculated using a random effects model.
Results
A total of 19 studies involving 6235 patients were included. The pooled mean %EWLs were 72.6% (95% CI 67.2–78.0,
I
2
= 97%); 67.1% (95% CI 61.7–72.6,
I
2
= 95%); and 59.1% (95% CI 48.8–69.4,
I
2
= 94%) at 1, 3, and 5 years, respectively. The pooled mean %TBWLs were 32.1%, 29.0%, and 25.5% at 1, 3, and 5 years, respectively. The pooled rates of revision due to gastroesophageal reflux disease and weight regain were 1.9% and 2.5%, respectively.
Conclusions
Our meta-analysis suggests that LSG is an effective procedure for weight reduction that offers durable response for up to 5 years among Asians with obesity. The longer-term data is needed.
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