Extra-abdominal infections caused by Comamonas kerstersii: Case report.

RATIONALE: Comamonas kerstersii mainly causes intra-abdominal infections with favorable outcomes due to high antibiotic susceptibility. We report the first case of pneumonia caused by C Kerstersii, which promoted patient death, and a second urinary tract infection by C Kerstersii with extensive drug resistance. PATIENT CONCERNS: A 46-year-old male (Case 1) with craniocerebral injury underwent emergency decompressive craniectomy, but his condition deteriorated further and presented with discontinuous fever, small moist rales on both lungs, and respiratory failure. Retrospective average nucleotide identity (ANI) analysis of the genomic sequence of the sputum isolate identified it as C Kerstersii 12322-1, antimicrobial susceptibility testing (AST) revealed that it was sensitive to 18 of 21 tested antibiotics.An 82-year-old male (Case 2) with hypertrophic prostate experienced gradual obstruction during urination, and a urine test revealed WBC ++. Retrospective ANI analysis of the urine isolate identified it as C Kerstersii 121606, which was resistant to 18 of 21 tested antibiotics. DIAGNOSES: Case 1 was diagnosed empirically as pneumonia caused by C Kerstersii strain 12322-1 secondary to craniocerebral injury and confirmed by retrospective ANI analysis; case 2 was diagnosed empirically as urinary infection secondary to prostate hyperplasia caused by C Kerstersii strain 121606 confirmed by the retrospective ANI analysis. INTERVENTIONS: Case 1 was administered cefoxitin, cefodizime, imipenem-cilastatin sodium, and underwent comprehensive salvage management. Case 2 was administered doxycycline alone. OUTCOMES: Case 1 died partially because of untimely identification of the responsible bacteria-12322-1. Case 2 was cured even 121606 exhibited an extensive drug resistance feature. LESSONS: Except for intra-abdominal infections with good prognosis, we verified that C Kerstersii could also cause extra-abdominal infections, such as the first pneumonia case and urinary infection. It could promote patient death; actual infections were underestimated due to identification difficulties, posing a health threat due to the presence of extensive drug resistance.

Ursolic acid ameliorates Nthy-ori 3-1 cells injury induced by IL-1ß through limiting MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway.

RATIONALE: Ursolic acid (UA) has exhibited anti-inflammatory and anti-oxidative drug effects. OBJECTIVES: In the research, we assessed the effects of UA on Nthy-ori 3-1 cells stimulated by IL-1ß and attempted to elucidate the mechanisms underlying the effects. METHODS: Autoimmune thyroiditis (AIT) was simulated using Nthy-ori 3-1 cells by IL-1ß (10 µM) treatment. UA (20 µM) was applied to ameliorate the injury of Nthy-ori 3-1 cells. The target of UA was predicted by TCMSP, BATMAN, and GEO database. Targeted relationship between lncRNA MALAT1 and miR-206, as well as miR-206 and PTGS1, was predicted by bioinformatics software and identified by dual luciferase assays. Cytokines in the cell supernatant and the apoptosis of cells were detected by ELISAs and flow cytometry assays, respectively. Expression levels of NF-κB signaling pathway-related proteins were estimated by western blot. RESULTS: By enquiring TCMSP, BATMAN, and GEO database, PTGS1 was identified as a target of UA. Afterward, a ceRNA network among MALAT1, miR-206, and PTGS1 was constructed. The expression levels of MALAT1 and PTGS1 in AIT tissues were obviously enhanced. Moreover, the ceRNA network formed by MALAT1/miR-206/PTGS1 contributed to the damage of Nthy-ori 3-1 cells induced by IL-1ß. However, UA ameliorated the Nthy-ori 3-1 cells injury induced by IL-1ß through mediating the MALAT1/miR-206/PTGS1 ceRNA network and NF-κB signaling pathway. CONCLUSIONS: UA treatment significantly relieved the injury of Nthy-ori 3-1 cells via inhibiting the ceRNA mechanism of MALAT1/miR-206/PTGS1 and inflammatory pathways, insinuating that UA may be helpful for the treatment of AIT.

First Report Cfr and Optr A Co-harboring Linezolid-Resistant Enterococcus faecalis in China.

A linezolid-resistant E.faecalis strain harboring optrA and cfr resistance genes were isolated from a patient in china, which had no mutations in rplC, rplD, rplV, and 23S rRNA gene. Transformation indicated that optrA and cfr were located on two different plasmids and both could be transferred to recipient strain, resulting in the increase of MICs of linezolid and chloramphenicol. Cfr, carried by an 11,872-bp plasmid, was enclosed with an IS110 transposase in upstream and an IS3-like transposase in downstream, while optrA was on an 8357-bp plasmid. As far as we know, this is the first report of an E.faecalis clinical strain co-harboring optrA and cfr in China.

Detection of 5 Kinds of Genes Related to Plasmid-Mediated Quinolone Resistance in Four Species of Nonfermenting Bacteria with 2 Drug Resistant Phenotypes.

OBJECTIVE: This study aimed to detect 5 kinds of genes related to plasmid-mediated quinolone resistance in four species of nonfermenting bacteria with 2 drug resistance phenotypes (multidrug resistance and pandrug resistance), which were Acinetobacter baumannii (Ab), Pseudomonas aeruginosa (Pa), Stenotrophomonas maltophilia (Sm), and Elizabethkingia meningoseptica (Em). METHODS: The Phoenix NMIC/ID-109 panel and API 20NE panel were applied to 19 isolated strains, including 6 Ab strains (2 strains with multidrug resistance and 4 strains with pandrug resistance), 6 Pa strains (3 strains with multidrug resistance and 3 strains with pandrug resistance), 4 Sm strains (2 strains with multidrug resistance and 2 strains with pandrug resistance), and 3 Cm strains (2 strains with multidrug resistance and 1 strain with pandrug resistance). After strain identification and drug susceptibility test, PCR was applied to detect 5 genes related to plasmid-mediated quinolone resistance. The genes detected were quinolone resistance A (qnrA), aminoglycoside acetyltransferase ciprofloxacin resistance variant, acc(6')-Ib-cr, and 3 integrons (intI1, intI2, and intI3). The amplified products were analyzed by 1% agarose gel electrophoresis and sequenced. Sequence alignment was carried out using the bioinformatics technique. RESULTS: Of 19 strains tested, 8 strains carried acc(6')-Ib-cr and 6 of them were of pandrug resistance phenotype (3 Ab strains, 2 Pa strains, and 1 Sm strain). The carrying rate of acc(6')-Ib-cr was 60.0% for strains of pandrug resistance (6/10). Two strains were of multidrug resistance (1 Ab strain and 1 Pa strain), and the carrying rate of acc(6')-Ib-cr was 22.0% (2/9). The carrying rate was significantly different between strains of multidrug resistance and pandrug resistance (P < 0.05). The class 1 integron was detected in 11 strains, among which 6 strains were of pandrug resistance (3 Ab strains, 2 Pa strains, and 1 Sm strain). The carrying rate of the class 1 integron was 60.0% (6/10). Five strains were of multidrug resistance (3 Pa strains, 1 Ab strain, and 1 Em strain), and the carrying rate was 55.6% (5/9). The carrying rate of the class 1 integron was not significantly different between strains of multidrug resistance and pandrug resistance (P > 0.05). Both acc(6')-Ib-cr and intI1 were detected in 6 strains, which were negative for qnrA, intI2, and intI3. CONCLUSION: Quinolone resistance of isolated strains was related to acc(6')-Ib-cr and intI1 but not to qnrA, intI2, or intI3. The carrying rate of acc(6')-Ib-cr among the strains of pandrug resistance was much higher than that among the strains of multidrug resistance. But, the strains of two drug resistant phenotypes were not significantly different in the carrying rate of intI1. The detection rates of the two genes were high and similar in Ab and Pa strains. 1 Em strain carried the class 1 integron.

KMT5A promotes metastasis of clear cell renal cell carcinoma through reducing cadherin-1 expression.

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of kidney cancer and is accompanied by a poor prognosis due to a high potential for metastasis and recurrence. The mechanism of ccRCC metastasis is not well known. N-lysine methyltransferase KMT5A serves a crucial role in the progression of human cancer; however, the function of KMT5A in the development of ccRCCs has not yet been investigated, which has triggered an interest in investigating the potential association between KMT5A and ccRCC. The present study demonstrates for the first time that KMT5A is a driving factor in ccRCC metastasis. The KMT5A expression level was revealed to be significantly higher in ccRCC tissues compared with adjacent normal tissues. Patients with ccRCC whose tumors expressed high levels of KMT5A were demonstrated to have significantly shorter postoperative survival times. In vitro knockdown of KMT5A expression in 786-O cells inhibited cell migration and invasion. KMT5A reduced cadherin-1 (CDH1) protein levels by directly inhibiting its transcription. The CDH1 mRNA levels were inversely correlated with KMT5A expression in ccRCC samples. Patients with high tumor KMT5A or low CDH1 levels had the poorest prognosis with the shortest overall survival (OS) time, and this combination was demonstrated to be an independent prognostic indicator for patient OS time in ccRCC, more accurate than monitoring KMT5A or CDH1 alone. Together, these results indicate that KMT5A serves a vital role in ccRCC development and progression, and it may be a novel target for ccRCC treatment and prevention.

The antibiotic resistance and pathogenicity of a multidrug-resistant Elizabethkingia anophelis isolate.

Elizabethkingia anophelis 12012-2 PRCM was isolated from a patient with multiple organ dysfunction syndrome and lower respiratory tract infection in China. Minimum inhibitory concentration (MIC) analysis demonstrated that it was resistant to 20 antibiotics including trimethoprim/sulfamethoxazole and ciprofloxacin, which were effective for the elimination of other Elizabethkingia infections. To investigate multidrug resistance and pathogenicity mechanisms, we analyzed genome features of 12012-2 PRCM and compared them to the other Elizabethkingia species. The draft genome size was 4.02 Mb with a GC content of 32%, comparable to that of other E. anophelis strains. Phylogenetic analysis showed that E. anophelis 12012-2 PRCM formed a sister group with E. anophelis 502, distinct from clades formed by other clinical and environmental E. anophelis isolates. E. anophelis 12012-2 PRCM contained multiple copies of ß-lactamase genes as well as genes predicted to function in antimicrobial efflux. It also contained 92 genes that were potentially involved in virulence, disease, and defense, and were associated with resistance and pathogenicity. Comparative genomic analysis showed high homology among three clinical and two environmental E. anophelis strains having a variety of similar antibiotic resistance and virulence factor genes, and similar genomic structure. Applications of this analysis will contribute to understanding the antibiotic resistance and pathogenic mechanisms of E. anophelis infections, which will assist in the management of infections as it increases in prevalence.

Comparative genomic analysis of Myroides odoratimimus isolates.

Myroides odoratimimus is an important nosocomial pathogen. Management of M. odoratimimus infection is difficult owing to the multidrug resistance and the unknown pathogenesis mechanisms. Based on our previous genomic sequencing data of M. odoratimimus PR63039 (isolated from a patient with the urinary tract infection), in this study, we further performed comparative genomic analysis for 10 selected Myroides strains. Our results showed that these Myroides genome contexts were very similar and phylogenetically related. Various prophages were identified in the four clinical isolate genomes, which possibly contributed to the genome evolution among the Myroides strains. CRISPR elements were only detected in the two clinical (PR63039 and CCUG10230) isolates and two environmental (CCUG12700 and H1bi) strains. With more stringent cutoff parameters in CARD analysis, the four clinical M. odoratimimus contained roughly equal antibiotic resistance genes, indicating their similar antibiotic resistance profiles. The three clinical (CCUG10230, CCUG12901, CIP101113) and three environmental (CCUG12700, L41, H1bi) M. odoratimimus strains were speculated to carry the indistinguishable virulent factors (VFs), which may involve in the similar pathogenesis mechanism. Moreover, some VFs might confer to the high capacity of dissemination, attacking tissue cells and induction of autoimmune complications. Our results facilitate the research of antibiotic resistance and the development of therapeutic regimens for the M. odoratimimus infections.

A performance evaluation of an immuno-latex chromatography card for the rapid detection of Candida spp.

This report evaluates the performance and species specificity of an immuno-latex chromatography card (ICC) for rapid detection of Candida spp. Double-manipulator single-blind Gram staining smear examination (GSSE) and ICC were used to analyze 354 vaginal discharge specimens (VDS) (including 98 tested as positive by GSSE) from women with suspected candidal vaginitis, simulated specimens with a concentration gradient, and vaginitis causing organism suspensions (0.9% NaCl) of 22 species from nine genera. Limit of detection, semi-quantitative detection performance, total detection performance and species specificity were determined for ICC, and the results were compared with those of the GSSE method. The limits of detection of ICC for Candida spp. in organism suspensions with 0.9% NaCl and simulated specimens were 7 × 106 cells/L and 7 × 108 cells/L respectively. For species specificity, the results were positive for six Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and C. guilliermondii) and negative for the remaining 16 species (C. lusitaniae, Saccharomyces cerevisiae; three Gram-positive coccus species, four Gram-negative bacillus species, three Gram-negative coccus species and four common microbes causing vaginal infection) from eight genera. The overall sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ICC for VDS were 93.81%, 99.10%, 97.31, 98.14% and 96.90%, respectively. The above indicators in the 98 VDS evaluated as positive were 84.39%, 92.86%, 86.74%, 96.72% and 70.27%, respectively. In summary, ICC offered better specificity, sensitivity, positive predictive value and negative predictive value for the detection of Candida spp. in VDS.

Correction to: Analysis of resistance genes of clinical Pannonibacter phragmitetus strain 31801 by complete genome sequencing.

Subsequent to publication it has been noticed that the below listed text parts, figures and tables of the above paper were taken from paper.

Analysis of resistance genes of clinical Pannonibacter phragmitetus strain 31801 by complete genome sequencing.

To clarify the resistance mechanisms of Pannonibacter phragmitetus 31801, isolated from the blood of a liver abscess patient, at the genomic level, we performed whole genomic sequencing using a PacBio RS II single-molecule real-time long-read sequencer. Bioinformatic analysis of the resulting sequence was then carried out to identify any possible resistance genes. Analyses included Basic Local Alignment Search Tool searches against the Antibiotic Resistance Genes Database, ResFinder analysis of the genome sequence, and Resistance Gene Identifier analysis within the Comprehensive Antibiotic Resistance Database. Prophages, clustered regularly interspaced short palindromic repeats (CRISPR), and other putative virulence factors were also identified using PHAST, CRISPRfinder, and the Virulence Factors Database, respectively. The circular chromosome and single plasmid of P. phragmitetus 31801 contained multiple antibiotic resistance genes, including those coding for three different types of ß-lactamase [NPS ß-lactamase (EC 3.5.2.6), ß-lactamase class C, and a metal-dependent hydrolase of ß-lactamase superfamily I]. In addition, genes coding for subunits of several multidrug-resistance efflux pumps were identified, including those targeting macrolides (adeJ, cmeB), tetracycline (acrB, adeAB), fluoroquinolones (acrF, ceoB), and aminoglycosides (acrD, amrB, ceoB, mexY, smeB). However, apart from the tripartite macrolide efflux pump macAB-tolC, the genome did not appear to contain the complete complement of subunit genes required for production of most of the major multidrug-resistance efflux pumps.

Analysis of resistance genes in pan-resistant Myroides odoratimimus clinical strain PR63039 using whole genome sequencing.

To clarify the antibiotic resistance mechanisms of Myroides odoratimimus, pan-resistant M. odoratimimus strain PR63039 was isolated and its genome sequenced and analyzed. Antimicrobial susceptibility testing was conducted using the Kirby-Bauer disk diffusion method, and the Phoenix-100 Automated Microbiology System with a NMIC/ID-4 panel including aminoglycosides, ß-lactams, polypeptides, quinolones, sulfonamides, chloramphenicols, and tetracyclines. Single-molecule real-time whole genome sequencing was conducted using the PacBio RSII system, and genome annotation was performed using RAST and IMG ER. To characterize the genome features, a number of databases and software programs, including GC-Profile, CG viewer, the VFDB database, ISfinder, RADB, CARD, ResFinder, and PHAST, were used. M. odoratimimus isolate PR63039 was resistant to almost all antibiotics tested, suggesting pan-drug resistance. The genome consisted of a 4,366,950-bp chromosome and a 90,798-bp plasmid (p63039), which contained a large number of resistance genes and virulence factors. The distribution of the resistance genes was distinctive, and a resistance region, designated MY63039-RR, was identified. RAST analysis indicated that 108 of the annotated genes were potentially involved in virulence, disease, and defense, all of which could be associated with resistance and pathogenicity. Prophage analysis also identified two incomplete prophages in the genome of M. odoratimimus PR63039. Multiple antibiotic-resistance genes were identified, including those associated with resistance to tetracycline (tetX), macrolides (ereB, cfrA, lasE), sulfonamides (sul2, sul3), ß-lactams (blaMUS-1, blaTUS-1, blaSFB-1, blaSLB-1, blaOXA-209, blaOXA-347), and chloramphenicol (cat). Further, the presence of 18 antibiotic efflux pump-encoding resistance genes, including acrB, acrD, acrF, adeB, adeG, adeJ, amrB, ceoB, cmeB, mdsB, mexB, mexD, mexF, mtrD, smeE, mdtF, macB, likely accounts for the observed quinolone resistance of strain PR63039. To the best of our knowledge, this is the first report of the presence of the blaSFB-1, blaSLB-1, blaOXA-209, blaOXA-347, and tetX resistance genes in M. odoratimimus.

Genomic insights of Pannonibacter phragmitetus strain 31801 isolated from a patient with a liver abscess.

Pannonibacter phragmitetus is a bioremediation reagent for the detoxification of heavy metals and polycyclic aromatic compounds (PAHs) while it rarely infects healthy populations. However, infection by the opportunistic pathogen P. phragmitetus complicates diagnosis and treatments, and poses a serious threat to immunocompromised patients owing to its multidrug resistance. Unfortunately, genome features, antimicrobial resistance, and virulence potentials in P. phragmitetus have not been reported before. A predominant colony (31801) was isolated from a liver abscess patient, indicating that it accounted for the infection. To investigate its infection mechanism(s) in depth, we sequenced this bacterial genome and tested its antimicrobial resistance. Average nucleotide identity (ANI) analysis assigned the bacterium to the species P. phragmitetus (ANI, >95%). Comparative genomics analyses among Pannonibacter spp. representing the different living niches were used to describe the Pannonibacter pan-genomes and to examine virulence factors, prophages, CRISPR arrays, and genomic islands. Pannonibacter phragmitetus 31801 consisted of one chromosome and one plasmid, while the plasmid was absent in other Pannonibacter isolates. Pannonibacter phragmitetus 31801 may have a great infection potential because a lot of genes encoding toxins, flagellum formation, iron uptake, and virulence factor secretion systems in its genome. Moreover, the genome has 24 genomic islands and 2 prophages. A combination of antimicrobial susceptibility tests and the detailed antibiotic resistance gene analysis provide useful information about the drug resistance mechanisms and therefore can be used to guide the treatment strategy for the bacterial infection.

Liver Abscess Caused by Pannonibacter phragmitetus: Case Report and Literature Review.

BACKGROUND: Bacterial hepatic abscess is a common occurrence in developing countries, which is mostly caused by Klebsiella pneumoniae and Escherichia coli. Pannonibacter phragmitetus is a Gram-negative alkali-tolerant bacillus that exists in the natural environment. Human infection by this bacterium is rare, with only four cases reported. METHOD: We presented one of these cases with a bacterial liver abscess by a polymicrobial infection involving P. phragmitetus and Streptococcus oralis, with P. phragmitetus being the predominate isolate. RESULT AND DISCUSSION: Our strain of P. phragmitetus was resistant to more antibiotics than the other reported two strains. This case further verified the infectivity of P. phragmitetus.

Elizabethkingia anophelis Isolated from Patients with Multiple Organ Dysfunction Syndrome and Lower Respiratory Tract Infection: Report of Two Cases and Literature Review.

Elizabethkingia anophelis, originally discovered from Anopheles mosquito gut, is an emerging pathogen, especially in immunocompromised patients. We isolated two strains of E. anophelis from two separate patients with multiple organ dysfunction syndrome and lower respiratory tract infection. In this paper, we reviewed the status of E. anophelis infection and its antibiotics resistance from reported cases.

Genomic analysis of the multi-drug-resistant clinical isolate Myroides odoratimimus PR63039.

Myroides odoratimimus (M. odoratimimus) has been gradually implicated as an important nosocomial pathogen that poses a serious health threat to immunocompromised patients owing to its multi-drug resistance. However, the resistance mechanism is currently unclear. To clarify the antibiotic resistance and infectivity mechanisms of M. odoratimimus, whole genome sequencing was performed on the multi-drug-resistant M. odoratimimus strain PR63039. The genome sequence was completed with single molecule real-time (SMRT) technologies. Then, annotation was performed using RAST and IMG-ER. A number of databases and software programs were used to analyze the genomic characteristics, including GC-Profile, ISfinder, CG viewer, ARDB, CARD, ResFinder, the VFDB database, PHAST and Progressive Mauve. The M. odoratimimus PR63039 genome consisted of a chromosome and a plasmid. The genome contained a large number of resistance genes and virulence factors. The distribution of the resistance genes was distinctive, and a resistance region named MY63039-RR was found. The subsystem features generated by RAST indicated that the annotated genome had 108 genes that were potentially involved in virulence, disease and defense, all of which had strong associations with resistance and pathogenicity. The prophage analysis showed two incomplete prophages in the genome. The genomic analysis of M. odoratimimus PR63039 partially clarified its antibiotic resistance mechanisms and virulence factors. Obtaining a clear understanding of its genomic characteristics will be conducive to the management of multidrug-resistant M. odoratimimus.

Serum Interleukin (IL)-9 and IL-10, but not T-Helper 9 (Th9) Cells, are Associated With Survival of Patients With Acute-on-Chronic Hepatitis B Liver Failure.

CD4 T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4 Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4 cells in peripheral blood. We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected. The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity.Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF.

Antibiotic resistance mechanisms of Myroides sp.

Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.

The Transforming Growth Factor ß1/Interleukin-31 Pathway Is Upregulated in Patients with Hepatitis B Virus-Related Acute-on-Chronic Liver Failure and Is Associated with Disease Severity and Survival.

The transforming growth factor ß1/interleukin-31 (TGF-ß1/IL-31) pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-ß1/IL-31 pathway in the cytopathic process of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-ß1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were analyzed among chronic hepatitis B (CHB) patients (n = 17), ACLF patients (n = 18), and normal control (NC) subjects (n = 18). Disease severity in patients with ACLF was assessed using the model for end-stage liver disease (MELD) and Child-Pugh scores. Serum TGF-ß1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22, and IL-33. In CHB and ACLF patients, serum levels of TGF-ß1 and IL-31 were both increased significantly compared with those in NC subjects and positively correlated with total bilirubin (TBil) and alpha-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-ß1 and IL-31, which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-ß1 and IL-31 levels. More importantly, serum levels of TGF-ß1 and IL-31 were markedly upregulated in ACLF nonsurvivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%, respectively) in predicting nonsurvival of ACLF patients. Increasing activity of the TGF-ß1/IL-31 pathway is well correlated with the extent of liver injury, disease severity, and nonsurvival of ACLF patients, while reducing activity is detected along the recovery from liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection.

Elevated TGF-ß1/IL-31 Pathway Is Associated with the Disease Severity of Hepatitis B Virus-Related Liver Cirrhosis.

The proinflammatory cytokines transforming growth factor beta 1 (TGF-ß1) and interleukin (IL)-31 have been implicated in tissue injury. However, whether TGF-ß1/IL-31 are stimulated and elevated in response to liver injury that leads to fibrogenesis in hepatitis B virus-related liver cirrhosis (HBV-LC) remains unclear. To investigate the association between TGF-ß1/IL-31 and stages of chronic HBV infection, serum TGF-ß1, IL-9, IL-10,IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were determined among patients with chronic hepatitis B (CHB; n=19), HBV-LC (n=20), and a normal control population (NC; n=18). Disease severity in patients with HBV-LC was assessed using model for end-stage liver disease (MELD) scores. Serum TGF-ß1 and IL-31 levels were strongly positively linked in all subjects, and both correlated positively with IL-22, IL-33, and IL-17. TGF-ß1 and IL-31 levels in the blood were both significantly higher in CHB and HBV-LC patients than in NC subjects. Elevated serum TGF-ß1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell count, and platelet levels. Serum TGF-ß1 and IL-31 were markedly higher in HBV-LC patients who did not have esophageal varices, and IL-31 had the highest sensitivity and specificity (90.9% and 66.7%, respectively) for indicating the absence of this complication. In summary, TGF-ß1 and IL-31 were linked to progression from CHB to LC, and correlated well with the severity of HBV-LC. These findings suggest possible roles of the TGF-ß1/IL-31 pathway in the pathogenesis of liver fibrosis during chronic HBV infection.

Ratios of regulatory T cells/T-helper 17 cells and transforming growth factor-ß1/interleukin-17 to be associated with the development of hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIM: The aim of this study is to evaluate the association of the regulatory T cells (Treg)/T-helper (Th) 17 cells and transforming growth factor-ß1 (TGF-ß1)/interleukin-17 (IL-17) ratios with the survival and disease progression in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). METHODS: The frequencies of Treg and Th17 cells were analyzed in 28 patients with HBV-LC, 70 patients with chronic hepatitis B (CHB) and 20 normal controls (NC) by flow cytometry. The levels of cytokines related to Treg/Th17 differentiation, including IL-10, TGF-ß1, IL-17, and IL-23, were measured by ELISA. RESULTS: Compared with NC, Treg cells were significantly increased in CHB patients and slightly increased in HBV-LC patients, whereas Th17 cells were markedly increased both in patients with CHB and HBV-LC. HBV-LC patients, especially the nonsurvival ones, manifested a profound decrease in the Treg/Th17 ratio, which was negatively correlated with Child-Pugh and model of end-stage liver disease scores. Serum IL-10, TGF-ß1, IL-17, and IL-23 levels were all significantly higher in HBV-LC patients than in NC. In addition, the TGF-ß1/IL-17 ratio was also markedly increased in patients with HBV-LC, especially in nonsurvival and decompensated liver cirrhosis patients, and positively correlated with total bilirubin, Child-Pugh, and model of end-stage liver disease scores. CONCLUSIONS: The decreased Treg/Th17 ratio and increased TGF-ß1/IL-17 ratio may be associated with the survival and disease progression in HBV-LC patients, and both of the two ratios can be used independently to predict the prognosis and disease progression of HBV-LC patients.