Pharmacological management of portal hypertension: current status and future

Gao, Zhu-Qing; Han, Ying; Li, Lei; Ding, Huiguo

doi:10.1097/cm9.0000000000001004

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…GERPs were used to evaluate the conservation of the variant locus. Rare putative pathogenic variants were filtered as follows ( Gao et al, 2020 ): the allele frequency of the candidate variant should be lower than 0.01 among 1000G, ExAC, ESP 6500, Genome Aggregation (GA) and Complete Genomics 46 (CG46) Databases ( Khanna and Sarin, 2019 ); amino acid changing variants were kept, and GERP scores should be higher than 2.0 ( Vilarinho et al, 2016 ); truncating variants were kept, and for missense variants, MCAP scores higher than 0.6 were automatically kept, whereas for other variants, the effect should be annotated as “Deleterious” or “Highly pathogenic” by at least two software programs for MCAP scores between 0.025 and 0.6. PKHD1 protein domain prediction was obtained using SMART ( Letunic et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

“…The single cell RNA sequencing analysis was implemented with Seurat package (Version 3.9.9). Cells were discarded according to the following criteria ( Gao et al, 2020 ): cells that had fewer than 400 genes (UMI >0) ( Khanna and Sarin, 2019 ); cells that had fewer than 600 UMI or over 10,000 UMI; and ( Vilarinho et al, 2016 ) cells that had more than 15% mitochondrial UMI counts. After the above quality control, for mouse kidney, human fetal kidney, human adult kidney and human liver scRNA-seq analysis, we performed log-normalization with the “vst” method and identified 2000, 3,000, 3,000 and 3,000 variable features, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Cirrhotic portal hypertension complicated esophageal-gastric variceal bleeding (EGVB), ascites, hepatic encephalopathy (HE), acute kidney injury (AKI) or hepatorenal syndrome (HRS) and splenomegaly accompanied by severe liver disfunctions, is almost accounted for 80–85%. In clinical practice, a small number of patients present with portal hypertension, such as splenomegaly and or EGVB, HE, their clinical manifestations are similar to the liver cirrhosis,but in fact, these patients do not have liver cirrhosis, that is non-cirrhotic portal hypertension (NCPH) ( Khanna and Sarin, 2019 ; Gao et al, 2020 ). Currently, chronic infections, autoimmune disorders, and genetic determinants have been reported to be associated with pathogenesis of NCPH ( Vilarinho et al, 2016 ; Wu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Liu

et al. 2021

Front. Genet.

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Background and Aims: The multiple renal cysts (MRC) occur in some patients with noncirrhotic portal hypertension (NCPH) could be a subset of ciliopathy. However, the potential genetic influencers and/or determinants in NCPH with MRC are largely unknown. The aim of this study was to explore the potential candidate variants/genes associated with those patients.Methods: 8,295 cirrhotic patients with portal hypertension were enrolled in cohort 1 and 267 patients affected with NCPH were included in cohort 2. MRC was defined as at least two cysts in both kidneys within a patient detected by ultrasonography or computed tomography. Whole-genome sequencing (WGS) was performed in nine patients (four from cohort 1 and five from cohort 2). Then we integrated WGS and publicly available single-cell RNA sequencing (scRNA-seq) to prioritize potential candidate genes. Genes co-expressed with known pathogenic genes within same cell types were likely associated NCPH with MRC.Results: The prevalence of MRC in NCPH patients (19.5%, 52/267) was significantly higher than cirrhotic patients (6.2%, 513/8,295). Further, the clinical characteristics of NCPH patients with MRC were distinguishable from cirrhotic patients, including late-onset, more prominent portal hypertension however having preserved liver functions. In the nine whole genome sequenced patients, we identified three patients with early onset harboring compound rare putative pathogenic variants in the known disease gene PKHD1. For the remaining patients, by assessing cilia genes profile in kidney and liver scRNA-seq data, we identified CRB3 was the most co-expressed gene with PKHD1 that highly expressed in ureteric bud cell, kidney stromal cell and hepatoblasts. Moreover, we found a homozygous variant, CRB3 p.P114L, that caused conformational changes in the evolutional conserved domain, which may associate with NCPH with MRC.Conclusion: ScRNA-seq enables unravelling cell heterogeneity with cell specific gene expression across multiple tissues. With the boosting public accessible scRNA-seq data, we believe our proposed analytical strategy would effectively help disease risk gene identification.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Liu

et al. 2021

Front. Genet.

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“…Various therapies may be used, such as anticoagulants in confirmed thrombosis cases, non-selective β-blockers, endoscopic ligation of varices in cirrhotic patients with large varicose veins or a risk of stigmata, implantation of a transjugular intrahepatic portosystemic shunt (TIPS) for acute variceal bleeding, antibiotics for peritonitis prevention, and other symptomatic treatments. The novel surgical-based therapy that has currently been developed is splenorenal shunt surgery (Gao et al 2020, Iwakiri & Trebicka 2021.…”

Section: Introductionmentioning

confidence: 99%

Efficacy, Safety, and Clinical Outcomes of Splenorenal Shunt Surgery as a Therapeutic Intervention for Portal Hypertension Patients

Yan Efrata Sembiring,

Heroe Soebroto,

Ito Puruhito

et al. 2023

FMI

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Highlights: 1. This study systematically reviewed the efficacy, clinical outcomes, and safety of the splenorenal shunt procedure with a comprehensive and meticulous approach.2. The splenorenal shunt procedure is an innovative surgical intervention that offers a viable option for the management of portal hypertension. Abstract Portal hypertension is the second most common gastrointestinal bleeding in cirrhosis and non-cirrhosis patients. The splenorenal shunt surgery is a potential intervention that may be considered for portal hypertension patients with clinical symptoms such as upper gastrointestinal bleeding caused by the rupture of gastro-esophageal varices. In this study, the researchers aimed to analyze the efficacy, clinical outcomes, and safety of splenorenal shunt surgery in portal hypertension patients. The sources were obtained from electronic search databases, including PubMed, Google Scholar, and ScienceDirect, using the keywords "Efficacy," "Safety," and "Clinical Outcomes." in relation to splenorenal shunt surgery in portal hypertension patients. The researchers set specific criteria for inclusion and exclusion to select the articles. This systematic review revealed the efficacy of the splenorenal shunt procedure with favorable outcomes. The success rate of splenorenal shunt surgery in reducing the clinical symptoms of portal hypertension varied between 66% and 100%. The prevailing complications observed in this study were shunt thrombosis, rebleeding, and thrombocytopenia. However, notable improvements could be achieved with general treatment. In terms of short- and long-term clinical outcomes, the splenorenal shunt procedure demonstrated favorable results. It can be concluded that splenorenal shunt surgery provides excellent clinical outcomes and should be considered a viable treatment option for patients with both cirrhotic and non-cirrhotic portal hypertension.

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Pharmacological management of portal hypertension: current status and future

Cited by 4 publications

References 18 publications

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Identification of Genetic Predisposition in Noncirrhotic Portal Hypertension Patients With Multiple Renal Cysts by Integrated Analysis of Whole-Genome and Single-Cell RNA Sequencing

Efficacy, Safety, and Clinical Outcomes of Splenorenal Shunt Surgery as a Therapeutic Intervention for Portal Hypertension Patients

Table1.DOC

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