Philipp Lutz1, Benjamin Krämer2, Dominik J Kaczmarek2, Marc P Hübner3, Bettina Langhans2, Beate Appenrodt4, Frank Lammert4, Jacob Nattermann2, Achim Hoerauf3, Christian P Strassburg2, Ulrich Spengler2, Hans Dieter Nischalke2. 1. Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany. Electronic address: philipp.lutz@ukb.uni-bonn.de. 2. Department of Internal Medicine I, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany. 3. Institute for Medical Microbiology, Immunology and Parasitology, University of Bonn, Bonn, Germany; German Center for Infection Research, Germany. 4. Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Abstract
BACKGROUND: Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52kDa (NDP52), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved. METHODS: Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis. RESULTS: Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52 rs2303015 minor variant in the derivation (p=0.04) and in the validation cohort (p=0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p=0.002) and the TLR2 -16934 TT variant (odds ratio 2.5, p=0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively. CONCLUSION: Presence of the NDP52 rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.
BACKGROUND: Spontaneous bacterial peritonitis is frequently a fatal infection in patients with liver cirrhosis. We investigated if nuclear dot protein 52kDa (NDP52), a negative regulator of toll-like receptor (TLR) signalling and autophagy adaptor protein, might be involved. METHODS: Two cohorts comprising 152 (derivation cohort) and 198 patients (validation cohort) with decompensated liver cirrhosis and 168 healthy controls were genotyped for the rs2303015 polymorphism in the NDP52 gene and prospectively followed-up for spontaneous bacterial peritonitis. RESULTS: Overall, 57 (38%) patients in the derivation cohort and 77 (39%) in the validation cohort had spontaneous bacterial peritonitis. Cirrhosis was due to alcohol abuse in 57% of the derivation and 66% of the validation cohort. In patients with alcoholic cirrhosis, patients with spontaneous bacterial peritonitis had an increased frequency of the NDP52rs2303015 minor variant in the derivation (p=0.04) and in the validation cohort (p=0.01). Multivariate analysis confirmed this minor variant (odds ratio 4.7, p=0.002) and the TLR2 -16934 TT variant (odds ratio 2.5, p=0.008) as risk factors for spontaneous bacterial peritonitis. In addition, presence of the NDP52 minor variant affected survival negatively. CONCLUSION: Presence of the NDP52rs2303015 minor variant increases the risk for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.
Authors: Philipp Lutz; Felix Goeser; Dominik J Kaczmarek; Stefan Schlabe; Hans Dieter Nischalke; Jacob Nattermann; Achim Hoerauf; Christian P Strassburg; Ulrich Spengler Journal: Dig Dis Sci Date: 2017-06-09 Impact factor: 3.199
Authors: Martina Mai; Sven Stengel; Eihab Al-Herwi; Jack Peter; Caroline Schmidt; Ignacio Rubio; Andreas Stallmach; Tony Bruns Journal: Sci Rep Date: 2017-07-07 Impact factor: 4.379
Authors: Edilmar Alvarado-Tapias; Carlos Guarner-Argente; Elida Oblitas; Elisabet Sánchez; Silvia Vidal; Eva Román; Mar Concepción; Maria Poca; Cristina Gely; Oana Pavel; Juan Camilo Nieto; Cándido Juárez; Carlos Guarner; Germán Soriano Journal: World J Hepatol Date: 2018-01-27