Dataset Information

Up-regulation of Plasma Hexosylceramide (d18: 1/18: 1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C: A 20-Year Cohort Study.

ABSTRACT: The aim of the present study was to explore the relationship between plasma sphingolipids and hepatitis C virus (HCV) replication in chronic hepatitis C (CHC) patients.A cohort of 120 treatment-naïve CHC patients was included. Liver biopsies and the Scheuer scoring system were used to assess hepatic inflammatory activity. Blood biochemical indicators, HCV-RNA load, and immunological markers were also measured. Forty-four plasma sphingolipids were identified and quantified using high-performance liquid chromatography-tandem mass spectrometry.The hexosylceramide (HexCer) (d18:1/18:1) level was significantly different between patients with a low HCV load (<10?IU/mL) and a high HCV load (?10?IU/mL), and it was positively correlated with the HCV-RNA load (r = 0.337, P = 0.001) in CHC patients. Additionally, the plasma HexCer (d18:1/18:1) level (odds ratio 1.302, 95% confidence interval 1.129-1.502) was an independent factor for a high HCV-RNA load. For patients with hepatic inflammation grade ?2 or HCV genotype 2, HexCer (d18:1/18:1) was independently related to a high HCV-RNA load.Plasma HexCer (d18:1/18:1) might be involved in the high viral replication level in chronic HCV infection, especially for CHC patients with genotype 2.

SUBMITTER: Zhang JY

PROVIDER: S-EPMC4907656 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Up-regulation of Plasma Hexosylceramide (d18: 1/18: 1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C: A 20-Year Cohort Study.

Zhang Jin-Yan JY Qu Feng F Li Jun-Feng JF Liu Mei M Ren Feng F Zhang Jing-Yun JY Bian Dan-Dan DD Chen Yu Y Duan Zhong-Ping ZP Zhang Jin-Lan JL Zheng Su-Jun SJ

Medicine 20160601 23

The aim of the present study was to explore the relationship between plasma sphingolipids and hepatitis C virus (HCV) replication in chronic hepatitis C (CHC) patients.A cohort of 120 treatment-naïve CHC patients was included. Liver biopsies and the Scheuer scoring system were used to assess hepatic inflammatory activity. Blood biochemical indicators, HCV-RNA load, and immunological markers were also measured. Forty-four plasma sphingolipids were identified and quantified using high-performance ...[more]

PMID: 27281078

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Project description:BackgroundHepatitis C virus (HCV)-infected patients require a specific continuum of care (CoC) from HCV screening to treatment. We assessed CoC of HCV-infected patients in a longitudinal study.MethodsWe established a cohort of subjects undergoing HCV screening (high alanine aminotransferase levels or risk factors) during preventive consultations at a French regional medical center from 1993 to 2013. Patients were considered to be HCV-infected if HCV RNA was detected in their serum. CoC was assessed as described by Viner et al. (Hepatology 2015): Stage 1, HCV screening; Stage 2, HCV RNA testing; Stage 3, continuing care; Stage 4, antiviral treatment. Cox multivariate analysis was performed to identify factors favoring CoC, defined as at least one course of antiviral treatment.ResultsIn total, 12,993 HCV tests were performed and 478 outpatients were found to be HCV-seropositive. We included 417 seropositive patients, after excluding false positives and patients lost to follow-up. The baseline characteristics of the patients were: sex ratio (M/F) 1.4; mean age 38.5 years; intravenous drug use (IDU) in 55%; and 28% in unstable social situations, estimated by the EPICES deprivation score. Antiviral treatment was initiated for 179 (42.9%) of the 379 (90.9%) patients attending specialist consultations. CoC was associated with screening after 1997 (HR 2.0, 95%CI 1.4-2.9), age > 45 years (HR 1.5, 95%CI 1.02-2.3), patient acceptance of care (HR 9.3, 95%CI 5.4-16.10), specialist motivation for treatment (HR 10.9, 95%CI 7.4-16.0), and absence of cancer (HR 6.7, 95%CI 1.6-27.9). Other comorbid conditions, such as depression and IDU, were not associated with CoC.ConclusionsOur 20-year cohort study reveals the real-life continuum of care for HCV-infected patients in France. The number of patients involved in HCV care after positive testing was substantial due to the organization of healthcare in France. An improved CoC along with new direct-acting antivirals should help to decrease chronic HCV infection.

Project description:BACKGROUND & AIMS:The 4 genotypes of hepatitis E virus (HEV) that infect humans (genotypes 1-4) vary in geographical distribution, transmission, and pathogenesis. Little is known about the properties of HEV or its hosts that contribute to these variations. Primary isolates grow poorly in cell culture; most studies have relied on variants adapted to cancer cell lines, which likely alter virus biology. We investigated the infection and replication of primary isolates of HEV in hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells. METHODS:Using a cell culture-adapted genotype 3 strain and primary isolates of genotypes 1 to 4, we compared viral replication kinetics, sensitivity to drugs, and ability of HEV to activate the innate immune response. We studied HLCs using quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence assay and enzyme-linked immunosorbent assays. We used an embryonic stem cell line that can be induced to express the CRISPR-Cas9 machinery to disrupt the peptidylprolyl isomerase A gene, encoding cyclophilin A (CYPA), a protein reported to inhibit replication of cell culture-adapted HEV. We further modified this line to rescue expression of CYPA before terminal differentiation to HLCs and performed HEV infection studies. RESULTS:HLCs were permissive for infection by nonadapted, primary isolates of HEV genotypes 1 to 4. HEV infection of HLCs induced a replication-dependent type III interferon response. Replication of primary HEV isolates, unlike the cell culture-adapted strain, was not affected by disruption of the peptidylprolyl isomerase A gene or exposure to the CYPA inhibitor cyclosporine A. CONCLUSIONS:Cell culture adaptations alter the replicative capacities of HEV. HLCs offer an improved, physiologically relevant, and genetically tractable system for studying the replication of primary HEV isolates. HLCs could provide a model to aid development of HEV drugs and a system to guide personalized regimens, especially for patients with chronic hepatitis E who have developed resistance to ribavirin.

Project description:BackgroundThe optimal treatment of acute, complete dislocation of the acromioclavicular joint (ACJ) is still unresolved.PurposeTo determine the difference between operative and nonoperative treatment in acute Rockwood types III and V ACJ dislocation.Study designRandomized controlled trial; Level of evidence, 2.MethodsIn the operative treatment group, the ACJ was reduced and fixed with 2 transarticular Kirschner wires and ACJ ligament suturing. The Kirschner wires were extracted after 6 weeks. Nonoperatively treated patients received a reduction splint for 4 weeks. At the 18- to 20-year follow-up, the Constant, University of California at Los Angeles Shoulder Rating Scale (UCLA), Larsen, and Simple Shoulder Test (SST) scores were obtained, and clinical and radiographic examinations of both shoulders were performed.ResultsTwenty-five of 35 potential patients were examined at the 18- to 20-year follow-up. There were 11 patients with Rockwood type III and 14 with type V dislocations. Delayed surgical treatment for ACJ was used in 2 patients during follow-up: 1 in the operatively treated group and 1 in the nonoperatively treated group. Clinically, ACJs were statistically significantly less prominent or unstable in the operative group than in the nonoperative group (normal/prominent/unstable: 9/4/3 and 0/6/3, respectively; P = .02) and in the operative type III (P = .03) but not type V dislocation groups. In operatively and nonoperatively treated patients, the mean Constant scores were 83 and 85, UCLA scores 25 and 27, Larsen scores 11 and 11, and SST scores 11 and 12 at follow-up, respectively. There were no statistically significant differences in type III and type V dislocations. In the radiographic analysis, the ACJ was wider in the nonoperative than the operative group (8.3 vs 3.4 mm; P = .004), and in the type V dislocations (nonoperative vs operative: 8.5 vs 2.4 mm; P = .007). There was no statistically significant difference between study groups in the elevation of the lateral end of the clavicle. Both groups showed equal levels of radiologic signs of ACJ osteoarthritis and calcification of the coracoclavicular ligaments.ConclusionNonoperative treatment was shown to produce more prominent or unstable and radiographically wider ACJs than was operative treatment, but clinical results were equally good in the study groups at 18- to 20-year follow-up. Both treatment methods showed statistically significant radiographic elevations of the lateral clavicle when compared with a noninjured ACJ.

Dataset Information

Up-regulation of Plasma Hexosylceramide (d18: 1/18: 1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C: A 20-Year Cohort Study.

Publications

Up-regulation of Plasma Hexosylceramide (d18: 1/18: 1) Contributes to Genotype 2 Virus Replication in Chronic Hepatitis C: A 20-Year Cohort Study.

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