Toll-like receptor (TLR) 2 promoter and intron 2 polymorphisms are associated with increased risk for spontaneous bacterial peritonitis in liver cirrhosis.

BACKGROUND & AIMS: Toll-like receptor (TLR) 2 and nucleotide-binding oligomerisation domain (NOD) 2 recognize distinct pathogen-associated molecular patterns (PAMS) on the cell surface and in the cytoplasm, respectively. Since they may contribute to susceptibility to spontaneous bacterial peritonitis (SBP), we studied the effects of TLR2 gene variants on susceptibility for SBP in relation to the previously reported NOD2 alleles. METHODS: Overall, 150 patients with liver cirrhosis and ascites were genotyped for TLR2 gene variants -16934 (rs4696480), Arg753Gln (rs5743708), Pro631His (rs5743704) and the TLR2 GT microsatellite polymorphism in intron 2. Patients were monitored for SBP over two years. TLR2 SNPs were identified by hybridization probe assays on a LightCycler system. Numbers of GT repeats were determined with an ABI310 sequencer and Genescan Analysis 2.1 software. RESULTS: Fifty two patients (35%) had SBP. Unlike the TLR2 Arg753Gln and Pro631His mutations, SBP was significantly more frequent in patients with the TLR2 -16934 TT genotype (38.5% vs. 15.3%; p = 0.002) and in carriers with two long tandem GT repeat alleles (>20) (53.8% vs. 25.5%; p = 0.001). A multivariate analysis confirmed TLR2 GT microsatellite polymorphism (OR = 3.8, p = 0.002) and NOD2 variants (OR = 3.3, p = 0.011) as independent predictors of SBP, and the simultaneous presence of both risk factors indicated a particularly high risk for SBP (OR = 11.3, p = 0.00002). CONCLUSIONS: Analogous to NOD2 risk variants, TLR2 polymorphisms indicate increased susceptibility toward SBP in cirrhotic patients with ascites, and the combination of the TLR2 GT microsatellite polymorphism with at least one NOD2 risk variant enables improved identification of patients with a high risk for SBP.

[Medical therapy of complications in liver cirrhosis]. / Medikamentöse Therapie der Komplikationen der Leberzirrhose.

Patients with liver cirrhosis bear a considerable risk of a variety of complications that involve virtually all organ systems. They can be addressed with a wide spectrum of drugs for acute interventions as well as for prophylactic purposes. At the same time treatment of the underlying disease, the identification and treatment of triggering factors and the possibility of liver transplantation should be kept in mind.

Lymphoid pneumonitis as an immune reconstitution inflammatory syndrome in a patient with CD4 cell recovery after HAART initiation.

In the era of highly active antiretroviral therapy (HAART), immune reconstitution inflammatory syndrome (IRIS) has come to present a significant clinical challenge. Following the recovery of memory T cells, latent infections may lead to clinical and laboratory deterioration despite immunological and virological reconvalescence. However, many other forms of complications after induction of HAART, which are not entirely understood, must be included in the entity of IRIS. Here we report a case of a patient complaining of respiratory distress and fever 10 days after initiating HAART. Radiologically and clinically, his findings mimicked Pneumocystis jiroveci pneumonia. However, no infectious agent could be detected, and bronchoalveolary lavage showed a high cell count (90% lymphocytes and 4% eosinophils) consistent with interstitial pneumonitis. He improved dramatically after treatment with oral steroids.

[Gastrointestinal bleeding in portal hypertension in liver cirrhosis]. / Die intestinale Blutung bei portaler Hypertension bei Leberzirrhose.

There are three major goals in the prophylaxis and treatment of upper gastrointestinal bleeding in portal hypertensive patients: prophylaxis of the first bleeding episode, therapy of active bleeding and prophylaxis of recurrent bleeding. Several therapeutic options are available: non-selective beta-blockers are the treatment of choice in the primary prophylaxis of the first bleeding episode in patients with large esophageal varices. Alternatively, endoscopic band ligation therapy is an option. Acute bleeding varices should be treated by ligation pharmacological and antibiotic therapy. Prophylaxis of recurrent bleeding is patient-dependent: shunt surgery is an option in young patients in a good medical condition (Child-Pugh class A). In patients with refractory ascites and a bilirubin below 3 mg/dl, TIPS is a good option together with recurrent bleeding. At the moment, there are no trials showing that endoscopic ligation therapy is superior to prevent pharmacological therapy. Nevertheless, the first-line treatment in most patients in Germany is endoscopic band ligation. Bleeding from ectopic varices and bleeding from hypertensive gastropathy should be treated individually either by endoscopy, TIPS or drug therapy.