The common genetic variants in IL-1Β and IL-1RN may have no predisposition to alcoholic liver disease: A meta-analysis

Abstract Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter. It is currently unknown if the rs2289669 locus is a cis-eQTL, which would validate its role as predictor of metformin efficacy. We looked at association between common genetic variants in the SLC47A1 gene region and HbA1c reduction after metformin treatment using locus-wise meta-analysis from the MetGen consortium. CRISPR-Cas9 was applied to perform allele editing of, or genomic deletion around, rs2289669 and of the closely linked rs8065082 in HepG2 cells. The genome-edited cells were evaluated for SLC47A1 expression and splicing. None of the common variants including rs2289669 showed significant association with metformin response. Genomic editing of either rs2289669 or rs8065082 did not alter SLC47A1 expression or splicing. Experimental and in silico analyses show that the rs2289669-containing haploblock does not appear to carry genetic variants that could explain its previously reported association with metformin efficacy.

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Genetic polymorphisms of cytochrome p4502E1 and susceptibility to alcoholic liver disease and hepatocellular carcinoma in a white population: a study and literature review, including meta-analysis

Molecular Pathology ◽

10.1136/mp.53.2.88 ◽

2000 ◽

Vol 53 (2) ◽

pp. 88-93 ◽

Cited By ~ 60

Author(s):

N A C S Wong

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Literature Review ◽

Genetic Polymorphisms ◽

Alcoholic Liver Disease ◽

Meta Analysis ◽

White Population ◽

Cytochrome P4502e1

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HFE genetic variability and risk of alcoholic liver disease: A meta-analysis

Journal of Huazhong University of Science and Technology [Medical Sciences] ◽

10.1007/s11596-016-1637-0 ◽

2016 ◽

Vol 36 (5) ◽

pp. 626-633

Author(s):

Yan-yan Xu ◽

Yu-han Tang ◽

Xiao-ping Guo ◽

Jing Wang ◽

Ping Yao

Keyword(s):

Liver Disease ◽

Genetic Variability ◽

Alcoholic Liver Disease ◽

Meta Analysis

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Reliability of Transient Elastography-Based Liver Stiffness for Diagnosing Portal Hypertension in Patients with Alcoholic Liver Disease: A Diagnostic Meta-Analysis with Specific Cut-Off Values

Ultraschall in der Medizin - European Journal of Ultrasound ◽

10.1055/a-0731-0178 ◽

2019 ◽

Vol 41 (01) ◽

pp. 60-68 ◽

Cited By ~ 5

Author(s):

Jinzhen Song ◽

Zida Ma ◽

Jianbo Huang ◽

Yan Luo ◽

Romanas Zykus ◽

...

Keyword(s):

Portal Hypertension ◽

Liver Disease ◽

Sensitivity And Specificity ◽

Alcoholic Liver Disease ◽

Transient Elastography ◽

Meta Analysis ◽

Liver Stiffness ◽

Cochrane Library ◽

Bivariate Model ◽

Disease Etiology

Abstract Background Transient elastography-based liver stiffness value (TE-LSV) has been studied for the diagnosis of portal hypertension. Liver stiffness is influenced by the disease etiology. We aimed to perform a meta-analysis to determine the performance of TE-LSV for diagnosing portal hypertension in patients with alcoholic liver disease (ALD). Methods We searched PubMed, Web of Science, Ovid and Cochrane library. A bivariate model was used to compute sensitivity and specificity. A random effects model was used to pool diagnostic odds ratios. Results 9 studies with 679 patients were included. The pooled sensitivity and specificity based on a cut-off value around 21.8 kPa for clinically significant portal hypertension (CSPH) were 0.89 (95 % confidence interval (CI), 0.83–0.93) and 0.71(95 % CI, 0.64–0.78), respectively. For severe portal hypertension (SPH), the pooled sensitivity and specificity for a cut-off value around 29.1 kPa were 0.88 (95 % CI, 0.83–0.92) and 0.74 (95 % CI, 0.67–0.81), respectively. Conclusion TE-LSV showed good performance for diagnosing portal hypertension in patients with ALD. The optimal cut-off value for CSPH and SPH was around 21.8 kPa and 29.1 kPa, respectively, and these two cut-off values showed good sensitivity and modest specificity. The etiology should be clear before using TE-LSV for portal hypertension.

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Mortality After Extrahepatic Gastrointestinal and Abdominal Wall Surgery in Patients With Alcoholic Liver Disease: A Systematic Review and Meta-Analysis

Alcohol and Alcoholism ◽

10.1093/alcalc/agaa043 ◽

2020 ◽

Vol 55 (5) ◽

pp. 497-511

Author(s):

Alfred Adiamah ◽

Lu Ban ◽

John Hammond ◽

Peter Jepsen ◽

Joe West ◽

...

Keyword(s):

Liver Disease ◽

Hospital Mortality ◽

Alcoholic Liver Disease ◽

Meta Analysis ◽

Gastrointestinal Surgery ◽

Secondary Analysis ◽

Postoperative Mortality ◽

Inclusion Criteria ◽

Number Of Patients ◽

Umbilical Hernia Repair

Abstract Aims This meta-analysis aimed to define the perioperative risk of mortality in patients with alcoholic liver disease (ALD) undergoing extrahepatic gastrointestinal surgery. Methods Systematic searches of Embase, Medline and CENTRAL were undertaken to identify studies reporting about patients with ALD undergoing extrahepatic gastrointestinal surgery published since database inception to January 2019. Studies were only considered if they reported on mortality as an outcome. Pooled analysis of mortality was stratified as benign and malignant surgery and specific operative procedures where feasible. Results Of the 2899 studies identified, only five studies met inclusion criteria, representing cholecystectomy (one study), umbilical hernia repair surgery (one study) and oesophagectomy (three studies). The total number of patients with ALD in these studies was 172. Therefore, any study on liver disease patients undergoing extrahepatic surgery that crucially included a subset with alcohol aetiology was included as a secondary analysis even though they failed to stratify mortality by underlying aetiology. The total number of studies that met this expanded inclusion criteria was 62, reporting on 37,703 patients with liver disease of which 1735 (4.5%) had a definite diagnosis of ALD. Meta-analysis of proportions of in-hospital mortality in patients with ALD undergoing upper gastrointestinal cancer surgery (oesophagectomy) was 23% [95% confidence interval (CI) 14–35%, I2 = 0%]. In-hospital mortality following oesophagectomy in liver disease patients of all aetiologies was lower, 14% (95% CI 9–21%, I2 = 41.1%). Conclusion Postoperative in-hospital mortality is high in patients with liver disease and ALD in particular. However, the currently available evidence on ALD is limited and precludes definitive conclusions on postoperative mortality risk.

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