ResearchPad - Hepatology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Influence of Besifovir Dipivoxil Maleate Combined with L-Carnitine on Hepatic Steatosis in Patients with Chronic Hepatitis B]]> https://www.researchpad.co/product?articleinfo=N9ea6741d-e264-47dc-befd-90a0488102c5 <![CDATA[Multicentre prospective observational study protocol for radiation exposure from gastrointestinal fluoroscopic procedures (REX-GI study)]]> https://www.researchpad.co/product?articleinfo=N6e40113f-39ef-4bd4-9268-97d309e1f1da

Introduction

Recently, the use of various endoscopic procedures under X-ray fluoroscopic guidance, such as endoscopic retrograde cholangiopancreatography (ERCP), interventional endoscopic ultrasonography (EUS), enteral endoscopy and stenting, has been rapidly increasing because of the minimally invasive nature of these procedures compared with that of surgical intervention. With the spread of CT and fluoroscopic interventions, including endoscopic procedures under X-ray guidance, high levels of radiation exposure (RE) from medical imaging have led to major concerns throughout society. However, information about RE related to these image-guided procedures in gastrointestinal endoscopy is scarce, and the RE reference levels have not been established. The aim of this study is to prospectively collect the actual RE dose and to help establish diagnostic reference levels (DRLs) in the field of gastroenterology in Japan.

Methods and analysis

This is a multicentre, prospective observational study that is being conducted to collect the actual RE from treatments and diagnostic procedures, including ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement. We will measure the total fluoroscopy time (min), the total dose–area product (Gycm2) and air-kerma (mGy) of those procedures. Because we are collecting the actual RE data and identifying the influential factors through a prospective, nationwide design, this study will provide guidance regarding the DRLs of ERCP, interventional EUS, balloon-assisted enteroscopy, enteral metallic stent placement and enteral tube placement.

Ethics and dissemination

Approval was obtained from the Institutional Review Board of Toyonaka Municipal Hospital (25 April 2019). The need for informed consent will be waived via the opt-out method of each hospital website.

Trial registration number

The UMIN Clinical Trials Registry, UMIN000036525.

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<![CDATA[Aberrant expression of two miRNAs promotes proliferation, hepatitis B virus amplification, migration and invasion of hepatocellular carcinoma cells: evidence from bioinformatic analysis and experimental validation]]> https://www.researchpad.co/product?articleinfo=N8f756cb8-5957-4c43-a86e-a428dcc762c2

Background

As key negative regulators of gene expression, microRNAs (miRNAs) play an important role in the onset and progression of hepatocellular carcinoma (HCC). This study aimed to identify the miRNAs involved in HCC carcinogenesis and their regulated genes.

Methods

The Gene Expression Omnibus (GEO) dataset (GSE108724) was chosen and explored to identify differentially expressed miRNAs using GEO2R. For the prediction of potential miRNA target genes, the miRTarBase was explored. Enrichment analysis of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed by the DAVID online tool. The hub genes were screened out using the CytoHubba plug-in ranked by degrees. The networks between miRNAs and hub genes were constructed by Cytoscape software. MiRNA mimics and negative control were transfected into HCC cell lines and their effects on proliferation, hepatitis B virus DNA (HBV-DNA) replication, TP53 expression, migration, and invasion were investigated. The following methods were employed: MTT assay, quantitative PCR (qPCR) assay, western blotting, wound healing assay, and transwell assay.

Results

A total of 50 differentially expressed miRNAs were identified, including 20 upregulated and 30 downregulated miRNAs, in HCC tumor tissues compared to matched adjacent tumor-free tissues. The top three upregulated (miR-221-3p, miR-222-3p, and miR-18-5p) and downregulated (miR-375, miR-214-3p and miR-378d) miRNAs, ranked by |log2 fold change (log2FC)|, were chosen and their potential target genes were predicted. Two gene sets, targeted by the upregulated and the downregulated miRNAs, were identified respectively. GO and KEGG pathway analysis showed that the predicted target genes of upregulated and downregulated miRNAs were mainly enriched in the cell cycle and cancer-related pathways. The top ten hub nodes of gene sets ranked by degrees were identified as hub genes. Analysis of miRNA-hub gene network showed that miR-221-3p and miR-375 modulated most of the hub genes, especially involving regulation of TP53. The q-PCR results showed that miR-221-3p and miR-375 were markedly upregulated and downregulated, respectively, in HCC cells and HCC clinical tissue samples compared to non-tumoral tissues. Furthermore, miR-221-3p overexpression significantly enhanced proliferation, HBV-DNA replication, as well as the migration and invasion of HCC cells, whereas miR-375 overexpression resulted in opposite effects. Western blotting analysis showed that the overexpression of miR-221-3p and miR-375 reduced and increased TP53 expression, respectively.

Conclusion

The present study revealed that miR-211-3p and miR-375 may exert vital effects on cell proliferation, HBV-DNA replication, cell migration, and invasion through the regulation of TP53 expression in HCC.

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<![CDATA[Hepatitis C elimination in the Netherlands (CELINE): study protocol for nationwide retrieval of lost to follow-up patients with chronic hepatitis C]]> https://www.researchpad.co/product?articleinfo=Ndd2f53d4-ac35-499b-93f3-028ca2c03331

Background

The Netherlands has a low hepatitis C virus (HCV) prevalence, estimated at 0.16%. Previous studies have shown that up to 30% of the diagnosed HCV population in the Netherlands has been lost to follow-up (LTFU). Retrieval of these patients could halt progression of liver disease in infected patients, reduce the number of infected individuals and limit HCV transmission. Several regional Dutch retrieval projects have already been executed, which demonstrated that retrieval is feasible. Therefore, we initiated a nationwide retrieval project, aiming to achieve microelimination in previously diagnosed but LTFU patients with chronic HCV through retrieval.

Methods

Laboratory records will be used to identify possible patients with chronic hepatitis C, defined as either a positive most recent HCV RNA or positive HCV antibodies without known RNA result. Reviewing patient records and obtaining current contact information from municipality databases will identify LTFU patients who are eligible for retrieval. These patients will be invited for outpatient clinic care. The primary outcome of the study is the total number of LTFU patients who have been successfully linked to care.

Discussion

Hepatitis C ELimination In the NEtherlands (CELINE) is within the remit of WHO elimination targets and the Dutch National Hepatitis Plan. The methodology of CELINE is based on previously conducted regional retrieval projects and is designed to overcome some of their limitations. After ethical approval was obtained in 2018, the first centre initiated retrieval in 2018 and the project is expected to finish in 2021.

Trial registration number

NCT04208035.

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<![CDATA[Association of Hepatitis B Virus DNA Level and Follow-up Interval With Hepatocellular Carcinoma Recurrence]]> https://www.researchpad.co/product?articleinfo=Ndaf115ef-b64b-4924-b46a-0c6f0b85ef0e

This prognostic study evaluates the feasibility and availability of a novel hepatitis B virus DNA index to assess the prognosis of patients with hepatitis B virus–related hepatocellular carcinoma.

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<![CDATA[Identification of exosomal miRNAs associated with the anthracycline-induced liver injury in postoperative breast cancer patients by small RNA sequencing]]> https://www.researchpad.co/product?articleinfo=Ne200efd1-a76e-4a00-891e-33814e709835

Background

Anthracycline-induced liver injury (AILI) is one of the serious complications of anthracycline-based adjuvant chemotherapy for postoperative breast cancer patients. Exosomal miRNAs, as signaling molecules in intercellular communication, play the essential roles in drug-induced liver injury (DILI). However, the expression profiles of them in patients with AILI remains unknown.

Methods

Seven post-chemotherapy patients were recruited in this study. After isolated plasma-derived exosomes, small RNA sequencing revealed exosomal miRNA profiles and differentially expressed miRNAs (DE-miRNAs) were identified between the liver injury group and non-liver injury group. miRTarBase and miRDB were used to predict the potential target genes of DE-miRNAs. DILI-related genes were downloaded from the CTD Database. The intersection of predicted genes and DILI-related genes were identified as the AILI-related target genes of the DE-miRNAs. GO annotation and KEGG pathway enrichment analysis were performed by the DAVID database. Furthermore, the protein-protein interaction (PPI) network was established by the STRING database and essential exosomal miRNAs were identified via Cytoscape software.

Results

A total of 30 DE-miRNAs and 79 AILI-related target genes were identified. AILI-related target genes of the DE-miRNAs are significantly enriched in NOD-like receptor signaling pathway, the HIF-1 signaling pathway, and the FoxO signaling pathway. Then, the hub genes were screened and we discovered that IL-6 and SOD2 are the most critical genes that may be involved in the development of AILI through the activation of immune response and the occurrence of oxidative stress, respectively. In addition, we found that miR-1-3p could potentially regulate most of the hub genes in the miRNA-hub gene network.

Conclusion

We explored the potential functions of DE-miRNAs and suggested exosomal miR-1-3p might be the essential exosomal miRNA in the pathogenesis of AILI. Moreover, our study provided an experimental basis for experimental verification to reveal the actual function and mechanism of miRNAs in AILI.

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<![CDATA[Ursolic acid improves the bacterial community mapping of the intestinal tract in liver fibrosis mice]]> https://www.researchpad.co/product?articleinfo=N8beab16a-fc77-4bbe-9676-10e62a380b31

Liver fibrosis often appears in chronic liver disease, with extracellular matrix (ECM) deposition as the main feature. Due to the presence of the liver-gut axis, the destruction of intestinal homeostasis is often accompanied by the development of liver fibrosis. The inconsistent ecological environment of different intestinal sites may lead to differences in the microbiota. The traditional Chinese medicine ursolic acid (UA) has been proven to protect the liver from fibrosis. We investigated the changes in the microbiota of different parts of the intestine during liver fibrosis and the effect of UA on these changes based on high-throughput sequencing technology. Sequencing results suggest that the diversity and abundance of intestinal microbiota decline and the composition of the microbiota is disordered, the potentially beneficial Firmicutes bacteria are reduced, and the pathways for functional prediction are changed in the ilea and anal faeces of liver fibrosis mice compared with normal mice. However, in UA-treated liver fibrosis mice, these disorders improved. It is worth noting that the bacterial changes in the ilea and anal faeces are not consistent. In conclusion, in liver fibrosis, the microbiota of different parts of the intestines have different degrees of disorder, and UA can improve this disorder. This may be a potential mechanism for UA to achieve anti-fibrosis. This study provides theoretical guidance for the UA targeting of intestinal microbiota for the treatment of liver fibrosis.

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<![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/product?articleinfo=N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

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<![CDATA[Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis]]> https://www.researchpad.co/product?articleinfo=Nd170950f-0b0f-46af-a42d-6b06a3bc49ed

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.

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<![CDATA[Toward precision prescribing for methadone: Determinants of methadone deposition]]> https://www.researchpad.co/product?articleinfo=N51499fe4-a854-40f2-ac0e-5bd2b114360f

Background

Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism.

Methods

We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants.

Results

Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI.

Conclusions

Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

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<![CDATA[Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations]]> https://www.researchpad.co/product?articleinfo=N8c4889da-2d62-467b-8b66-b271dff2cf8d

Objective

A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.

Methods

A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.

Results

Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.

Discussion

Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.

Registration

CRD42017060473.

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<![CDATA[Nomograms for predicting overall survival and cancer-specific survival in young patients with pancreatic cancer in the US based on the SEER database]]> https://www.researchpad.co/product?articleinfo=Nc163a081-e30a-4539-9d1d-f30b97862201

Background

The incidence of young patients with pancreatic cancer (PC) is on the rise, and there is a lack of models that could effectively predict their prognosis. The purpose of this study was to construct nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) of young patients with PC.

Methods

PC patients younger than 50 years old from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were selected and randomly divided into training set and validation set. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent factors affecting OS. The Fine and Gray competing risk regression model was used to determine the independent factors affecting CSS. We used significant variables in the training set to construct nomograms predicting prognosis. The discrimination and calibration power of models were evaluated by concordance index (C-index), calibration curve and 10-flod cross-validation.

Results

A total of 4,146 patients were selected. Multivariable Cox analysis showed that gender, race, grade, pathological types, AJCC stage and surgery were independent factors affecting OS. The C-index of the nomogram predicting OS in training and validation was 0.733 (average = 0.731, 95% CI [0.724–0.738]) and 0.742 (95% CI [0.725–0.759]), respectively. Competing risk analysis showed that primary site, pathological types, AJCC stage and surgery were independent factors affecting CSS. The C-index of the nomogram predicting CSS in training and validation set was 0.792 (average = 0.765, 95% CI [0.742–0.788]) and 0.776 (95% CI [0.773–0.779]), respectively. C-index based on nomogram was better in training and validation set than that based on AJCC stage. Calibration curves showed that these nomograms could accurately predict the 1-, 3- and 5-year OS and CSS both in training set and validation set.

Conclusions

The nomograms could effectively predict OS and CSS in young patients with PC, which help clinicians more accurately and quantitatively judge the prognosis of individual patients.

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<![CDATA[Severe hyperbilirubinemia is associated with higher risk of contrast-related acute kidney injury following contrast-enhanced computed tomography]]> https://www.researchpad.co/product?articleinfo=N624c57d4-8983-4ece-aecc-e0e7860066cf

Introduction

Contrast-induced acute kidney injury (CI-AKI) is associated with high risks of morbidity and mortality. Hyperbilirubinemia might have some renal protection but with no clear cutoff value for protection. Related studies are typically on limited numbers of patients and only in conditions of vascular intervention.

Methods

We performed this study to elucidate CI-AKI in patients after contrast-enhanced computed tomography (CCT). The outcomes were CI-AKI, dialysis and mortality. Patients were divided to three groups based on their serum levels of total bilirubin: ≤1.2 mg/dl, 1.3–2.0 mg/dl, and >2.0 mg/dl.

Results

We enrolled a total of 9,496 patients who had received CCT. Patients with serum total bilirubin >2.0 mg/dl were associated with CI-AKI. Those undergoing dialysis had the highest incidence of PC-AKI (p<0.001). No difference was found between the two groups of total bilirubin ≤1.2 and 1.3–2.0 mg/dl. Patients with total bilirubin >2mg/dl were associated with CI-AKI (OR = 1.89, 1.53–2.33 of 95% CI), dialysis (OR = 1.40, 1.01–1.95 of 95% CI) and mortality (OR = 1.63, 1.38–1.93 of 95% CI) after adjusting for laboratory data and all comorbidities (i.e., cerebrovascular disease, coronary artery disease, peripheral arterial disease, and acute myocardial infarction, diabetes mellitus, hypertension, gastrointestinal bleeding, cirrhosis, peritonitis, ascites, hepatoma, shock lung and colon cancer). We concluded that total bilirubin level >2 mg/dl is an independent risk factor for CI-AKI, dialysis and mortality after CCT. These patients also had high risks for cirrhosis or hepatoma.

Conclusion

This is the first study providing evidence that hyperbilirubinemia (total bilirubin >2.0 mg/dl) being an independent risk factor for CI-AKI, dialysis and mortality after receiving CCT. Most patients with total bilirubin >2.0mg/dl had cirrhosis or hepatoma.

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<![CDATA[Acute liver failure]]> https://www.researchpad.co/product?articleinfo=Nb08f88d8-2ff1-4e20-8fed-1eed760dafd9

Acute liver failure in children is a rare but potentially fatal disease. Causes of ALF in neonatal period are different from those in early or late childhood. Despite the improvement in the paediatric intensive care, liver transplantation remains the only effective treatment. Use of newer treatment modalities (liver assist devices and hepatocyte transplantation) is still in experimental phase. Management requires early recognition, prompt diagnosis of treatable condition, supportive therapy and prevention of complications hence these children should ideally be treated in a specialist unit.

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<![CDATA[Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation]]> https://www.researchpad.co/product?articleinfo=N830fd982-5721-4069-a58e-12904d852b76

Background

Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death.

Methods

We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016.

Results

The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM.

Conclusion

Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

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<![CDATA[Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma]]> https://www.researchpad.co/product?articleinfo=Nbefbdee0-3f34-4b48-86f3-7ca275dff284

Background

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis and a high incidence. The molecular changes and novel biomarkers of HCC need to be identified to improve the diagnosis and prognosis of this disease. We investigated the current research concentrations of HCC and identified the transcriptomics-related biomarkers of HCC from The Cancer Genome Atlas (TGCA) database.

Methods

We investigated the current research concentrations of HCC using literature metrology analysis for studies conducted from 2008 to 2018. We identified long noncoding RNAs (lncRNAs) that correlated with the clinical features and survival prognoses of HCC from The Cancer Genome Atlas (TGCA) database. Differentially expressed genes (lncRNAs, miRNAs, and mRNAs) were also identified by TCGA datasets in HCC tumor tissues. A lncRNA competitive endogenous RNA (ceRNA) network was constructed from lncRNAs based on intersected lncRNAs. Survival times and the association between the expression levels of the key lncRNAs of the ceRNA network and the clinicopathological characteristics of HCC patients were analyzed using TCGA. Real-time polymerase chain reaction (qRT-PCR) was used to validate the reliability of the results in tissue samples from 20 newly-diagnosed HCC patients.

Results

Analysis of the literature pertaining to HCC research revealed that current research is focused on lncRNA functions in tumorigenesis and tumor development. A total of 128 HCC dysregulated lncRNAs were identified; 66 were included in the co-expressed ceRNA network. We analyzed survival times and the associations between the expression of 66 key lncRNAs and the clinicopathological features of the HCC patients identified from TCGA. Twenty-six lncRNAs were associated with clinical features of HCC (P < 0.05) and six key lncRNAs were associated with survival time (log-rank test P < 0.05). Six key lncRNAs were selected for the validation of their expression levels in 20 patients with newly diagnosed HCC using qRT-PCR. Consistent fold changes in the trends of up and down regulation between qRT-PCR validation and TCGA proved the reliability of our bioinformatics analysis.

Conclusions

We used integrative bioinformatics analysis of the TCGA datasets to improve our understanding of the regulatory mechanisms involved with the functional features of lncRNAs in HCC. The results revealed that lncRNAs are potential diagnostic and prognostic biomarkers of HCC.

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<![CDATA[The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia]]> https://www.researchpad.co/product?articleinfo=Neac843bb-be68-4ed5-ae78-d8fdce066c1d

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

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<![CDATA[Identification and validation of potential key long noncoding RNAs in sorafenib-resistant hepatocellular carcinoma cells]]> https://www.researchpad.co/product?articleinfo=Nc22deb9b-a695-4f48-b2d5-0a5632539383

As the first-line treatment, sorafenib has been used for advanced hepatocellular carcinoma (HCC), but the chemoresistance commonly restricts to the clinical efficiency. In this study, we intend to investigate the genome-wide expression pattern of long noncoding RNAs (lncRNAs) in sorafenib-resistant HCC. Herein, we identified thousands of differentially expressed lncRNAs in sorafenib-resistant HCC cells by high-throughput sequencing compared to the parental. Besides, based on GO (Gene Ontology) term enrichment analysis, these differentially expressed lncRNAs are mainly related to binding and catalytic activity and biological regulation of metabolic processes in both the sorafenib-resistant Huh7 cells (Huh7-S) and sorafenib-resistant HepG2 cells (HepG2-S) compared to the parental cells. Moreover, when analyzed by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway, the differentially expressed genes were significantly related to the tight junction. Among them, the expression of TCONS_00284048 and TCONS_00006019 was consistently up-regulated in sorafenib-resistant HCC cell lines, whereas when either was knocked down, the sensitivity of Huh7-S and HepG2-S cells to sorafenib was increased. Taken together, our data demonstrate that the lncRNA expression profile is significantly altered in sorafenib-resistant HCC cells as well as differentially expressed lncRNAs may play crucial functions on HCC sorafenib resistance and HCC progression.

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<![CDATA[Using transjugular intrahepatic portosystemic shunt as the first‐line therapy in secondary prophylaxis of variceal hemorrhage]]> https://www.researchpad.co/product?articleinfo=Nf6f53f89-9338-46a9-b8c7-632f6fb3c9e7

Abstract

Background and Aim

This study aims to evaluate and compare the survival and other portal hypertension‐related complications of patients with portal pressure gradient (PPG) ≥ 25 mmHg using transjugular intrahepatic portosystemic shunt (TIPS) as the first‐line and second‐line therapies in secondary prophylaxis of variceal hemorrhage.

Methods

Fifty patients diagnosed with liver cirrhosis were enrolled in this retrospective study, with 35 of whom received TIPS as the first‐line therapy in secondary prophylaxis of variceal hemorrhage and 15 of whom as second‐line treatment. We observed and analyzed the survival, occurrence of variceal rebleeding and hepatic encephalopathy (HE) of patients in the two groups during the follow up.

Results

The technical success rate was 100%. In a median follow‐up time of 12 (1–37) and 15 (2–27) months, respectively, significant statistical difference was observed between the first‐line group and the second‐line group concerning cumulative survival rate (94.3% vs 66.7%, log–rank P = 0.01). But that was not the case when it comes to the cumulative rate of variceal rebleeding (8.6% vs 26.7%, log–rank P = 0.164) and HE (22.9% vs 20.0%, log–rank P = 0.793). And multivariate analysis indicated that group assignment (hazard ratio = 8.250, 95% confidence interval = 1.383–49.213, P = 0.021) was the only predictor of survival. Interestingly, we found that spleen diameter (hazard ratio = 0.578, 95% confidence interval = 0.393–0.849, P = 0.005) could be regarded as independent predictor of the occurrence of HE.

Conclusions

For patients with PPG ≥ 25 mmHg who have recovered from an episode of acute esophageal variceal hemorrhage, utilizing TIPS as the first‐line therapy to prevent rebleeding is demonstrated effective in improving the survival and therefore should be recommended to a wider range of clinical practice.

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<![CDATA[Polyploidy spectrum: a new marker in HCC classification]]> https://www.researchpad.co/product?articleinfo=N726e8a10-a8d1-4404-861b-91f4685f379d

Objectives

Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investigated whether a specific ploidy spectrum is associated with clinical and molecular features of HCC.

Design

Ploidy spectra were determined on surgically resected tissues from patients with HCC as well as healthy control tissues. To define ploidy profiles, a quantitative and qualitative in situ imaging approach was used on paraffin tissue liver sections.

Results

We first demonstrated that polyploid hepatocytes are the major components of human liver parenchyma, polyploidy being mainly cellular (binuclear hepatocytes). Across liver lobules, polyploid hepatocytes do not exhibit a specific zonation pattern. During liver tumorigenesis, cellular ploidy is drastically reduced; binuclear polyploid hepatocytes are barely present in HCC tumours. Remarkably, nuclear ploidy is specifically amplified in HCC tumours. In fact, nuclear ploidy is amplified in HCCs harbouring a low degree of differentiation and TP53 mutations. Finally, our results demonstrated that highly polyploid tumours are associated with a poor prognosis.

Conclusions

Our results underline the importance of quantification of cellular and nuclear ploidy spectra during HCC tumorigenesis.

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