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Article ; Online: In Acute Severe Ulcerative Colitis Patients Who Receive Rescue Therapy, Prior Maintenance Therapy and Day 3 C-Reactive Protein After Rescue Therapy Are Associated With 12-Month Colectomy Risk.

Sninsky, Jared A / Staicu, Ana-Maria / Barnes, Edward L

2023

Language	English
Publishing date	2023-09-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1340971-2
ISSN	1536-4844 ; 1078-0998
ISSN (online)	1536-4844
ISSN	1078-0998
DOI	10.1093/ibd/izad215
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Article ; Online: Impact of patatin-like phospholipase-3 (rs738409 C>G) polymorphism on fibrosis progression and steatosis in chronic hepatitis C.

Trépo, Eric / Pradat, Pierre / Potthoff, Andrej / Momozawa, Yukihide / Quertinmont, Eric / Gustot, Thierry / Lemmers, Arnaud / Berthillon, Pascale / Amininejad, Leila / Chevallier, Michéle / Schlué, Jerome / Kreipe, Hans / Devière, Jacques / Manns, Michael / Trépo, Christian / Sninsky, John / Wedemeyer, Heiner / Franchimont, Denis / Moreno, Christophe

Hepatology (Baltimore, Md.)

2011 Volume 54, Issue 1, Page(s) 60–69

Abstract: Unlabelled: Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and ... a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis ... centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and ...

Abstract	Unlabelled: Only 20% of patients with chronic hepatitis C (CHC) will develop cirrhosis, and fibrosis progression remains highly unpredictable. A recent genome-wide association study identified a genetic variant in the patatin-like phospholipase-3 (PNPLA3) gene (rs738409 C>G) associated with steatosis that was further demonstrated to influence severity of fibrosis in nonalcoholic fatty liver disease. The aim of this study was to assess the impact of this polymorphism on histological liver damage and response to antiviral therapy in CHC. We recruited 537 Caucasian CHC patients from three European centers (Brussels, Belgium [n = 229]; Hannover, Germany [n = 171]; Lyon, France [n = 137]); these patients were centrally genotyped for the PNPLA3 (rs738409 C>G) polymorphism. We studied the influence of rs738409 and other variants in the PNPLA3 region on steatosis and fibrosis assessed both in a cross-sectional and longitudinal manner. Seven other variants previously associated with fibrosis progression were included. Finally, we explored the impact of rs738409 on response to standard antiviral therapy using the interferon lambda 3 (IL28B) [rs12979860 C>T] variant both as a comparator and as a positive control. After adjustment for age, sex, body mass index, alcohol consumption, and diabetes, rs738409 mutant G allele homozygote carriers remained at higher risk for steatosis (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.08-6.03, P = 0.034), fibrosis (OR 3.13, 95% CI 1.50-6.51, P = 0.002), and fibrosis progression (OR 2.64, 95% CI 1.22-5.67, P = 0.013). Conversely, rs738409 was not independently associated with treatment failure (OR 1.07, 95% CI 0.46-2.49, P = 0.875) and did not influence clinical or biological variables. Conclusion: The PNPLA3 (rs738409 C>G) polymorphism favors steatosis and fibrosis progression in CHC. This polymorphism may represent a valuable genetic predictor and a potential therapeutic target in CHC liver damage.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/therapeutic use ; Belgium ; Cross-Sectional Studies ; Disease Progression ; Fatty Liver/genetics ; Fatty Liver/pathology ; Fatty Liver/physiopathology ; Female ; France ; Genetic Predisposition to Disease/genetics ; Germany ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/physiopathology ; Humans ; Interferons ; Interleukins/therapeutic use ; Lipase/genetics ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Liver Cirrhosis/physiopathology ; Longitudinal Studies ; Male ; Membrane Proteins/genetics ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Treatment Outcome ; White People/genetics
Chemical Substances	Antiviral Agents ; interferon-lambda, human ; Interleukins ; Membrane Proteins ; Interferons (9008-11-1) ; Lipase (EC 3.1.1.3) ; adiponutrin, human (EC 3.1.1.3)
Language	English
Publishing date	2011-04-13
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.24350
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Article ; Online: Role of a cirrhosis risk score for the early prediction of fibrosis progression in hepatitis C patients with minimal liver disease.

Trépo, Eric / Potthoff, Andrej / Pradat, Pierre / Bakshi, Rakesh / Young, Bradford / Lagier, Robert / Moreno, Christophe / Verset, Laurine / Cross, Richard / Degré, Delphine / Lemmers, Arnaud / Gustot, Thierry / Berthillon, Pascale / Rosenberg, William / Trépo, Christian / Sninsky, John / Adler, Michael / Wedemeyer, Heiner

Journal of hepatology

2011 Volume 55, Issue 1, Page(s) 38–44

Abstract: Background & aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly ...

Abstract	Background & aims: Fibrosis progression in patients with chronic hepatitis C (CHC) is highly variable. A Cirrhosis Risk Score (CRS) based on seven genetic variants has been recently developed for identifying patients at risk for cirrhosis. The objective of this study was to assess the role of the CRS for the early prediction of fibrosis progression in CHC patients with mild liver fibrosis. In addition, we evaluated the potential benefit, for prediction accuracy, of a recently described non-invasive fibrosis staging assay, the Enhanced Liver Fibrosis (ELF) test. Methods: Two separate cohorts of HCV patients (Brussels, Belgium/Hannover, Germany) were retrospectively analyzed. Only patients with a fibrosis Ishak or METAVIR score of F0-F1 at baseline were included. Patients were classified as progressors if they showed an increase ≥2 fibrosis stages at the second histological evaluation after a follow-up ≥5years. The CRS was calculated locally. Genotyping was performed by PCR and oligonucleotide ligation with the resulting signal detected with a Luminex® 200TM and computer analysis. Results: In Brussels, 12/25 patients progressed (48%); similarly in Hannover, 16/31 (52%) patients progressed. In both sample sets, the CRS was significantly associated with fibrosis progression (p=0.050 in Brussels; p=0.018 in Hannover). The ELF test was only a significant predictor in Hannover (p=0.015). In multivariate analysis the CRS remained the only variable associated with fibrosis progression (odds-ratio=2.23, 95%CI 1.21-4.11 p=0.01). Conclusions: Although conducted on a limited number of patients, this study in two independent centres confirms that the CRS predicts fibrosis progression in initially mild CHC.
MeSH term(s)	Cohort Studies ; Disease Progression ; Female ; Genetic Variation ; Hepatitis C, Chronic/classification ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/pathology ; Humans ; Liver Cirrhosis/classification ; Liver Cirrhosis/etiology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Male ; Middle Aged ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Risk Factors
Language	English
Publishing date	2011-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2010.10.018
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Article ; Online: An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C.

O'Brien, Thomas R / Everhart, James E / Morgan, Timothy R / Lok, Anna S / Chung, Raymond T / Shao, Yongwu / Shiffman, Mitchell L / Dotrang, Myhanh / Sninsky, John J / Bonkovsky, Herbert L / Pfeiffer, Ruth M

PloS one

2011 Volume 6, Issue 7, Page(s) e20904

Abstract: ... response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data ... from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype ... and clinical variables.: Methods: HALT-C enrolled patients with advanced CHC who had failed ...

Abstract	Background: Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. Methods: HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). Results: Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. Conclusion: A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.
MeSH term(s)	Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Area Under Curve ; Demography ; Female ; Genotype ; Hepacivirus/drug effects ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/virology ; Humans ; Interferons ; Interleukins/genetics ; Male ; Middle Aged ; Models, Biological ; Polymorphism, Single Nucleotide/genetics ; Ribavirin/pharmacology ; Ribavirin/therapeutic use ; Treatment Outcome
Chemical Substances	Antiviral Agents ; interferon-lambda, human ; Interleukins ; Ribavirin (49717AWG6K) ; Interferons (9008-11-1)
Language	English
Publishing date	2011-07-08
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0020904
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Article ; Online: Predicting cirrhosis and clinical outcomes in patients with advanced chronic hepatitis C with a panel of genetic markers (CRS7).

Curto, Teresa M / Lagier, Robert J / Lok, Anna S / Everhart, James E / Rowland, Charles M / Sninsky, John J

Pharmacogenetics and genomics

2011 Volume 21, Issue 12, Page(s) 851–860

Abstract: ... hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously ... Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori ... of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis ...

Abstract	Objectives: Genetic factors may play a role in fibrosis progression in patients with chronic hepatitis C (CHC). A cirrhosis risk score (CRS7) with seven single nucleotide polymorphisms was previously shown to correlate with cirrhosis in patients with CHC. This study aimed to assess the validity of CRS7 as a marker of fibrosis progression and cirrhosis and as a predictor of clinical outcomes in patients with CHC. Methods: A total of 938 patients (677 Caucasians, 165 African-Americans, and 96 Hispanic/Other) in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial were studied. CRS7 was categorized a priori as high risk (n=440), medium risk (n=310), or low risk (n=188). Patients were assessed for four possible outcomes: fibrosis progression, cirrhosis, clinical outcomes [decompensation or hepatocellular carcinoma (HCC)], or HCC alone. Results: Twenty-nine percent (142/493) developed an increase in fibrosis score by greater than or equal to 2 points on follow-up biopsies, 58% had cirrhosis on one or more biopsies, 35% developed at least one clinical outcome, and 13% developed HCC. CRS7 (trend test) was associated with risk for fibrosis progression (P=0.04) with adjusted hazard ratio of 1.27 (95% confidence interval: 1.01-1.58) and with cirrhosis (P=0.05) with adjusted odds ratio of 1.19 (1.00-1.41). Rates of HCC and clinical outcomes were increased in patients with higher CRS7 scores, but were not statistically significant (P=0.12 clinical outcomes, and P=0.07 HCC). A single nucleotide polymorphism in AZIN1 was significantly associated with fibrosis progression. Conclusion: CRS7 was validated as a predictor of fibrosis progression and cirrhosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, who all had advanced fibrosis. CRS7 was not predictive of clinical outcome.
MeSH term(s)	Antiviral Agents/therapeutic use ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Cohort Studies ; Disease Progression ; Female ; Genetic Markers ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/pathology ; Humans ; Interferon-alpha/therapeutic use ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Male ; Middle Aged ; Polyethylene Glycols/therapeutic use ; Polymorphism, Single Nucleotide ; Prospective Studies ; Recombinant Proteins/therapeutic use ; Treatment Outcome
Chemical Substances	Antiviral Agents ; Genetic Markers ; Interferon-alpha ; Recombinant Proteins ; Polyethylene Glycols (3WJQ0SDW1A) ; peginterferon alfa-2a (Q46947FE7K)
Language	English
Publishing date	2011-09-27
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	2175826-8
ISSN	1744-6880 ; 0960-314X ; 1744-6872
ISSN (online)	1744-6880
ISSN	0960-314X ; 1744-6872
DOI	10.1097/FPC.0b013e32834c3e74
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Article: Identification of two gene variants associated with risk of advanced fibrosis in patients with chronic hepatitis C.

Gastroenterology

2006 Volume 130, Issue 6, Page(s) 1679–1687

Abstract: ... and age at infection do not accurately predict which patients with chronic hepatitis C (CHC ...

Abstract	Background & aims: Previously identified clinical risk factors such as sex, alcohol consumption, and age at infection do not accurately predict which patients with chronic hepatitis C (CHC) will develop advanced fibrosis (bridging fibrosis and cirrhosis). The aim of this study was to identify genetic polymorphisms that can predict the risk of advanced fibrosis in patients with CHC. Methods: A total of 916 subjects with CHC was enrolled from 2 centers. A gene-centric disease association study of 24,832 putative functional, single nucleotide polymorphisms (SNPs) was performed. Of the 1609 SNPs that were significantly associated (P </= .05) with advanced fibrosis in the discovery cohort (University of California San Francisco [UCSF], N = 433), the first batch of 100 SNPs were selected for validation in the replication cohort (Virginia Commonwealth University [VCU], N = 483).<br />Results: A missense SNP in the DEAD box polypeptide 5 (DDX5) gene was significantly associated with an increased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 1.8 and 2.2, respectively). Two diplotype groups, carrying the haplotypes composed of the DDX5 SNP and 2 neighboring POLG2 SNPs were also significantly associated with an increased risk of advanced fibrosis and had comparable or better risk estimates. In addition, a missense SNP in the carnitine palmitoyltransferase 1A (CPT1A) gene was associated with a decreased risk of advanced fibrosis in both the UCSF and the VCU cohorts (OR, 0.3 and 0.6, respectively). Conclusions: Subjects with CHC carrying DDX5 minor allele or DDX5-POLG2 haplotypes are at an increased risk of developing advanced fibrosis, whereas those carrying the CPT1A minor allele are at a decreased risk.
MeSH term(s)	Adolescent ; Adult ; Aged ; Alleles ; DEAD-box RNA Helicases ; Disease Progression ; Female ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Haplotypes ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/pathology ; Heterozygote ; Humans ; Liver Cirrhosis/genetics ; Liver Cirrhosis/pathology ; Male ; Middle Aged ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide/genetics ; Probability ; Prognosis ; Prospective Studies ; Protein Kinases/genetics ; RNA Helicases/genetics ; Risk Assessment ; Sensitivity and Specificity ; Severity of Illness Index
Chemical Substances	Protein Kinases (EC 2.7.-) ; Ddx5 protein, human (EC 3.6.1.-) ; DEAD-box RNA Helicases (EC 3.6.4.13) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2006-05
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2006.02.032
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Article ; Online: A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis.

Paris, Andrew J / Snapir, Zohar / Christopherson, Cindy D / Kwok, Shirley Y / Lee, Ursula E / Ghiassi-Nejad, Zahra / Kocabayoglu, Peri / Sninsky, John J / Llovet, Josep M / Kahana, Chaim / Friedman, Scott L

Hepatology (Baltimore, Md.)

2011 Volume 54, Issue 6, Page(s) 2198–2207

Abstract: Unlabelled: Among several single-nucleotide polymorphisms (SNPs) that correlate with fibrosis progression in chronic HCV, an SNP in the antizyme inhibitor (AzI) gene is most strongly associated with slow fibrosis progression. Our aim was to identify the ...

Abstract	Unlabelled: Among several single-nucleotide polymorphisms (SNPs) that correlate with fibrosis progression in chronic HCV, an SNP in the antizyme inhibitor (AzI) gene is most strongly associated with slow fibrosis progression. Our aim was to identify the mechanism(s) underlying this observation by exploring the impact of the AzI SNP on hepatic stellate cell (HSC) activity. Seven novel AZIN1 splice variants ("SV2-8") were cloned by polymerase chain reaction from the LX2 human HSC line. Expression of a minigene in LX2 containing the AZIN1 slow-fibrosis SNP yielded a 1.67-fold increase in AZIN1 splice variant 2 (AZIN1 SV2) messenger RNA (mRNA) (P = 0.05). In healthy human leukocytes, the SNP variant also correlated with significantly increased SV2 mRNA. Cells (293T) transfected with short hairpin RNA (shRNA) complementary to the exonic splicing chaperone SRp40 expressed 30% less SRp40 (P = 0.044) and 43% more AzI SV2 (P = 0.021) than control shRNA-expressing cells, mimicking the effect of the sequence variant. LX2 cells transfected with AZIN1 full-length complementary DNA expressed 35% less collagen I mRNA (P = 0.09) and 18% less α-smooth muscle actin mRNA (P = 0.09). Transient transfection of AZIN1 SV2 complementary DNA into LX2 cells reduced collagen I gene expression by 64% (P = 0.001) and α-smooth muscle actin by 43% (P = 0.005) compared to vector-transfected controls, paralleling changes in protein expression. Both AZIN1 and AZIN-SV2 mRNAs are detectable in normal human liver and reduced in HCV cirrhotic livers. The AZIN1-SV2 acts via a polyamine-independent pathway, as it neither interacts with antizyme nor affects the ability of AZIN1 lacking this variant to neutralize antizyme. Conclusion: An SNP variant in the AZIN1 gene leads to enhanced generation of a novel alternative splice form that modifies the fibrogenic potential of HSCs.
MeSH term(s)	Adult ; Alternative Splicing ; Carrier Proteins/genetics ; Collagen Type I/biosynthesis ; Enzyme Inhibitors/metabolism ; Female ; Hepatic Stellate Cells/metabolism ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/genetics ; Humans ; Liver Cirrhosis/metabolism ; Liver Cirrhosis/prevention & control ; Male ; Middle Aged ; Ornithine Decarboxylase/genetics ; Polymorphism, Single Nucleotide ; Transfection
Chemical Substances	AZIN1 protein, human ; Carrier Proteins ; Collagen Type I ; Enzyme Inhibitors ; Ornithine Decarboxylase (EC 4.1.1.17)
Language	English
Publishing date	2011-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.24608
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Article ; Online: An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C.

Thomas R O'Brien / James E Everhart / Timothy R Morgan / Anna S Lok / Raymond T Chung / Yongwu Shao / Mitchell L Shiffman / Myhanh Dotrang / John J Sninsky / Herbert L Bonkovsky / Ruth M Pfeiffer / HALT-C Trial Group

PLoS ONE, Vol 6, Iss 7, p e

2011 Volume 20904

Abstract: ... response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data ... from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype ... and clinical variables. METHODS:HALT-C enrolled patients with advanced CHC who had failed previous ...

Abstract	BACKGROUND:Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS:HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). RESULTS:Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION:A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.
Keywords	Medicine ; R ; Science ; Q
Subject code	310
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.

Li, Yonghong / Chang, Monica / Abar, Olivia / Garcia, Veronica / Rowland, Charles / Catanese, Joseph / Ross, David / Broder, Samuel / Shiffman, Mitchell / Cheung, Ramsey / Wright, Teresa / Friedman, Scott L / Sninsky, John

Journal of hepatology

2009 Volume 51, Issue 4, Page(s) 750–757

Abstract: ... hepatitis C virus. Other variants in these loci have not been examined but may be associated with fibrosis risk ...

Abstract	Background/aims: Seven genomic loci, implicated by single nucleotide polymorphisms (SNPs), have recently been associated with progression to advanced fibrosis (fibrosis risk) in patients with chronic hepatitis C virus. Other variants in these loci have not been examined but may be associated with fibrosis risk independently of or due to linkage disequilibrium with the original polymorphisms. Methods: We carried out dense genotyping and association testing of additional SNPs in each of the 7 regions in Caucasian case control samples. Results: We identified several SNPs in the toll-like receptor 4 (TLR4) and syntaxin binding protein 5-like (STXBP5L) loci that were associated with fibrosis risk independently of the original significant SNPs. Haplotypes consisting of these SNPs in TLR4 and STXBP5L were strongly associated with fibrosis risk (global P=3.04 x 10(-5) and 4.49 x 10(-6), respectively). Conclusions: Multiple variants in TLR4 and STXBP5L genes modulate risk of liver fibrosis. These findings are of relevance for understanding the pathogenesis of HCV-induced liver disease in Caucasians and may be extended to other ethnicities as well.
MeSH term(s)	Adaptor Proteins, Vesicular Transport ; Carrier Proteins/genetics ; Case-Control Studies ; European Continental Ancestry Group/genetics ; Genome-Wide Association Study ; Haplotypes ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/genetics ; Hepatitis C, Chronic/immunology ; Humans ; Linkage Disequilibrium ; Liver Cirrhosis/etiology ; Liver Cirrhosis/genetics ; Liver Cirrhosis/immunology ; Polymorphism, Single Nucleotide ; Risk Factors ; Toll-Like Receptor 4/genetics
Chemical Substances	Adaptor Proteins, Vesicular Transport ; Carrier Proteins ; STXBP5L protein, human ; TLR4 protein, human ; Toll-Like Receptor 4
Language	English
Publishing date	2009-06-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605953-3
ISSN	1600-0641 ; 0168-8278
ISSN (online)	1600-0641
ISSN	0168-8278
DOI	10.1016/j.jhep.2009.04.027
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Article: The end of "Cutting for Stone"? Using the lithoclast trilogy for cystolitholapaxy on a 4 cm bladder stone per urethra.

Sninsky, Brian C / Flamiatos, Jason F / Nakada, Stephen Y

Urology case reports

2019 Volume 26, Page(s) 100964

Abstract: We present a case of cystolitholapaxy using the LithoClast Trilogy lithotripter device per urethra via a rigid 26F nephroscope in a 36-year-old female with chondrodysplasia, paraplegia, contractures, and history of bladder augment managed with clean ... ...

Abstract	We present a case of cystolitholapaxy using the LithoClast Trilogy lithotripter device per urethra via a rigid 26F nephroscope in a 36-year-old female with chondrodysplasia, paraplegia, contractures, and history of bladder augment managed with clean intermittent catheterization. The stone was 4cm in diameter with an average of 1300 Hounsfield Units, and composed of 45% calcium phosphate, 40% struvite, and 15% ammonium urate. Advantages include faster fragmentation time versus holmium laser, improved safety with suction extraction and improved vision, ability to treat larger stones endoscopically, and control of all variables by one surgeon with only a single foot pedal.
Language	English
Publishing date	2019-07-10
Publishing country	United States
Document type	Case Reports
ZDB-ID	2745459-9
ISSN	2214-4420
ISSN	2214-4420
DOI	10.1016/j.eucr.2019.100964
Database	MEDical Literature Analysis and Retrieval System OnLINE

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