Spelling suggestions: "subject:"nichtalkoholische fettleberhepatitis"" "subject:"nichtalkoholische betweenhepatitis""
1 |
Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR SpectroscopyKarlas , Thomas, Wiegand, Johannes 07 May 2014 (has links) (PDF)
Introduction: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease
(NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP)
correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a headto-
head comparison between both methods.
Methods: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient
elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2
34–66%, S3 $67%.
Results: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated
with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiveroperating
characteristics curves were 0.93 vs. 0.88 for steatosis $S1 and 0.94 vs. 0.88 for $S2, respectively. Boot-strapping
analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for
the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total
cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity
of 100% and 98.1% at a cut-off value of 8.85 kPa.
Conclusion: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification.
Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive
characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects,
anthropometry, and presence of advanced liver fibrosis.
|
2 |
Die Rolle der Einzelnukleotid-Polymorphismen rs10754558 und rs35829419 des NLRP3-Inflammasoms bei der nichtalkoholischen Fettlebererkrankung / The role of the single nucleotide polymorphisms rs10754558 and rs35829419 of the NLRP3 inflammasome in non-alcoholic fatty liver diseasePaukstat, Katrin January 2022 (has links) (PDF)
Die vorliegende Dissertation hat sich mit der Fragestellung beschäftigt, inwiefern die Einzelnukleotid-Polymorphismen (kurz SNP) rs10754558 und rs35829419 des NLRP3-Gens mit einer Suszeptibilität für eine NAFL und/oder NASH assoziiert sind.
Die Studienkohorte bestand aus 202 Teilnehmern der Würzburger NAFLD-Kohorte der Universitätsklinik Würzburg, 159 NAFLD-Patienten, die im Rahmen der Fettlebersprechstunde der Universitätsklinik Würzburg behandelt wurden und 43 gesunde Kontrollen. Voraussetzung für die Aufnahme in das Patientenkollektiv der durch die Ethikkomission genehmigten Studie war zuallererst die Aufklärung und Zustimmung des Patienten, außerdem eine klinisch oder histologisch diagnostizierte Fettlebererkrankung. Sekundäre Ursachen einer Fettleber oder andere Lebererkrankungen waren Ausschlusskriterien. Alle Teilnehmer erhielten eine Blutentnahme, 97 NAFLD-Patienten eine Leberbiopsie, davon 10 perkutan und 87 subkapsulär im Zuge einer bariatrischen OP. Die Genotypisierung übernahm das Labor der Universitätsklinik Homburg, die weiteren Analysen der Blutwerte, der peripheren und intrahepatischen Immunzellen und die Begutachtung der Leber-Histologie fanden an der Universitätsklinik Würzburg im Rahmen eines vorherigen Forschungsvorhabens statt (Rau et al., 2016).
Für beide SNPs war das Hardy-Weinberg-Equilibrium im Studien- sowie Patientenkollektiv erfüllt. Zwischen den einzelnen Genotypen und dem Vorliegen einer NAFL und/oder NASH fanden sich für beide SNPs keine signifikanten Zusammenhänge. Für den Wildtyp CC des SNP rs10754558 ergaben sich in der Studienkohorte signifikant höhere AST-Mediane (p=0,018) und häufiger hochnormale (in den oberen 20 % des Normbereichs) ALT-Werte (p=0,02) im Vergleich zu den Genotypen CG und GG. Hier lässt sich über eine protektive Rolle des Minor Allels in Bezug auf Leberwerterhöhungen spekulieren. Da bisher die Funktion von rs10754558 im NLRP3-Gen noch nicht ausreichend erforscht ist, sollten Untersuchungen auf transkriptioneller Ebene folgen und Studien mit anderen Polymorphismen des NLRP3-Gens und mit NAFLD-assoziierter Gene durchgeführt werden, um eine mögliche Assoziation mit anderen für die Entwicklung der NAFLD relevanten SNPs nicht zu übersehen.
In der Analyse mit den Entzündungswerten zeigten sich für die Genotypen CG und GG signifikant erhöhte Frequenzen von Th1-Zellen im peripheren Blut (p=0,003). Zusätzlich lässt sich das vermehrte Vorkommen von Th1-Zellen auch im Rahmen der bestehenden Adipositas bzw. des metabolischen Syndroms im Sinne einer low grade inflammation interpretieren (s. Diskussion). Immerhin sind 95 % der NAFLD-Patienten der Studienkohorte von Adipositas betroffen.
Die Ergebnisse zu SNP rs35829419, einer gain-of-function Variante im NLRP3-Gen, waren nur eingeschränkt beurteilbar, da keine homozygoten Allel-A-Träger vorlagen und die Stichprobenzahl für die Analyse der intrahepatischen Immunzellen viel zu gering war, um aussagekräftig sein zu können. In der gesamten Kohorte stellte sich ein signifikanter Zusammenhang zwischen dem heterozygoten Genotyp von rs35829419 und einer erhöhten Frequenz an Th2-Zellen (p=0,024) im peripheren Blut heraus. Innerhalb der NAFLD gingen frühere Studien bisher eher von einer Th1-dominierten Immunantwort aus (Bertola et al., 2010), wenn nicht gar einer Th2-Defizienz (Guebre-Xabier et al., 2000). Das hier vorliegende Ergebnis könnte immerhin auf eine höhere entzündliche Aktivität bei Minor-Allelträgern hindeuten. Die weitere Untersuchung mit größeren Stichproben und weiteren Polymorphismen, die in der NAFLD-Pathogenese bekanntermaßen eine Rolle spielen, erscheint auch für den SNP rs35829419 sinnvoll.
Im Hinblick auf die zunehmende Prävalenz der NAFLD als Volkskrankheit der westlichen Welt wird die personalisierte Medizin, inklusive Prävention, Diagnostik und Therapie immer mehr an Bedeutung zunehmen. Die Identifizierung von genetischen Risikovarianten, die an der Pathogenese der NAFLD beteiligt sind, ist ein erster Schritt auf dem Weg hin zu besseren Therapiemöglichkeiten. / This dissertation has dealt with the question of the extent to which the single nucleotide polymorphisms (SNP) rs10754558 and rs35829419 of the NLRP3 gene are associated with susceptibility to NAFL and/or NASH.
The study cohort consisted of 202 participants of the Würzburg NAFLD cohort of the University Hospital Würzburg, 159 NAFLD patients who were treated during the fatty liver consultation hours of the University Hospital Würzburg and 43 healthy controls. The prerequisite for inclusion in the patient population of the study approved by the ethics committee was first and foremost the information and consent of the patient, as well as a clinically or histologically diagnosed fatty liver disease. Secondary causes of fatty liver or other liver diseases were exclusion criteria. All participants received a blood sample, 97 NAFLD patients a liver biopsy, of which 10 percutaneously and 87 subcapsular in the course of bariatric surgery. The genotyping was carried out by the laboratory of the University Hospital Homburg, the further analyses of the blood values, the peripheral and intrahepatic immune cells and the assessment of the liver histology took place at the University Hospital Würzburg as part of a previous research project (Rau et al., 2016).
For both SNPs, the Hardy Weinberg equilibrium was fulfilled in the study and patient collective. There were no significant associations between the individual genotypes and the presence of NAFL and/or NASH for either SNP. For the wild type CC of SNP rs10754558, significantly higher AST medians (p=0.018) and more frequently highly normal (in the upper 20% of the normal range) ALT values (p=0.02) were found in the study cohort compared to the genotypes CG and GG. Here one can now speculate about a protective role of the minor allele with regard to liver value increases. Since the function of rs10754558 in the NLRP3 gene has not yet been sufficiently researched, studies at the transcriptional level should follow and studies with other polymorphisms of the NLRP3 gene and with NAFLD-associated genes should be carried out in order not to overlook a possible association with other SNPs relevant for the development of NAFLD.
The analysis with the inflammation values showed significantly increased frequencies of Th1 cells in peripheral blood for the genotypes CG and GG (p=0.003). In addition, the increased occurrence of Th1 cells can also be interpreted in the context of existing obesity or metabolic syndrome in the sense of low-grade inflammation (see discussion). After all, 95% of NAFLD patients in the study cohort are affected by obesity.
The results for SNP rs35829419, a gain-of-function variant in the NLRP3 gene, could only be assessed to a limited extent because there were no homozygous allele A carriers and the sample number for the analysis of intrahepatic immune cells was far too small to be meaningful. Throughout the cohort, there was a significant association between the heterozygous genotype of rs35829419 and an increased frequency of Th2 cells (p=0.024) in peripheral blood. Within NAFLD, previous studies have tended to assume a Th1-dominated immune response (Bertola et al., 2010 ), if not Th2 deficiency (Guebre-Xabier et al., 2000). The present result could at least indicate a higher inflammatory activity in minor allele carriers. Further investigation with larger samples and other polymorphisms, which are known to play a role in NAFLD pathogenesis, would also be useful for SNP rs35829419.
In view of the increasing prevalence of NAFLD as a widespread disease in the Western world, personalized medicine, including prevention, diagnostics, and therapy, will become increasingly important. The identification of genetic risk variants involved in the pathogenesis of NAFLD is a first step towards better treatment options.
|
3 |
Non-Invasive Assessment of Hepatic Steatosis in Patients with NAFLD Using Controlled Attenuation Parameter and 1H-MR SpectroscopyKarlas, Thomas, Wiegand, Johannes January 2014 (has links)
Introduction: Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease
(NAFLD). 1H-Magnetic resonance spectroscopy (1H-MRS) and the ultrasound-based controlled attenuation parameter (CAP)
correlate with biopsy proven steatosis, but have not been correlated with each other so far. We therefore performed a headto-
head comparison between both methods.
Methods: Fifty patients with biopsy-proven NAFLD and 15 healthy volunteers were evaluated with 1H-MRS and transient
elastography (TE) including CAP. Steatosis was defined according to the percentage of affected hepatocytes: S1 5-33%, S2
34–66%, S3 $67%.
Results: Steatosis grade in patients with NAFLD was S1 36%, S2 40% and S3 24%. CAP and 1H-MRS significantly correlated
with histopathology and showed comparable accuracy for the detection of hepatic steatosis: areas under the receiveroperating
characteristics curves were 0.93 vs. 0.88 for steatosis $S1 and 0.94 vs. 0.88 for $S2, respectively. Boot-strapping
analysis revealed a CAP cut-off of 300 dB/m for detection of S2-3 steatosis, while retaining the lower cut-off of 215 dB/m for
the definition of healthy individuals. Direct comparison between CAP and 1H-MRS revealed only modest correlation (total
cohort: r = 0.63 [0.44, 0.76]; NAFLD cases: r = 0.56 [0.32, 0.74]). For detection of F2–4 fibrosis TE had sensitivity and specificity
of 100% and 98.1% at a cut-off value of 8.85 kPa.
Conclusion: Our data suggest a comparable diagnostic value of CAP and 1H-MRS for hepatic steatosis quantification.
Combined with the simultaneous TE fibrosis assessment, CAP represents an efficient method for non-invasive
characterization of NAFLD. Limited correlation between CAP and 1H-MRS may be explained by different technical aspects,
anthropometry, and presence of advanced liver fibrosis.
|
Page generated in 0.6968 seconds