Perdita Wietzke-Braun

Interleukin-29 uses a type 1 interferon-like program to promote antiviral responses in human hepatocytes†

Interleukin‐28A (IL‐28A), IL‐28B and IL‐29 are a family of class II cytokines that stimulate antiviral responses through a heterodimeric receptor that is distinct from the type I interferon (IFN) receptor. To better understand how this newly described family of cytokines regulates the antiviral state, we compared various cellular responses elicited by IL‐29 and IFN‐α. Here we show that these cytokines stimulate similar patterns of signal transducer and activator of transcription 1 (STAT‐1), ‐2, ‐3, and ‐5 phosphorylation and nearly identical patterns of gene expression when analyzed in two distinct cell types by microarray analysis. Interestingly, the IL‐29 receptor is preferentially expressed on primary hepatocytes within normal liver and pegylated forms of IL‐29 and IFN‐α induced equivalent 2′5′ oligoadenylate synthetase (OAS) and MX1 gene expression in this cell type. Pegylated IL‐29 also produced a significant reduction in human hepatitis B and hepatitis C viral load in vitro and reduced the cytopathic effect caused by the fully replicating flavivirus, West Nile virus. In conclusion, IL‐29 and IFN‐α stimulate identical antiviral responses despite their utilization of different receptors. This fact, combined with significant receptor expression in hepatitis virus‐infected livers, suggests that IL‐29 may have therapeutic value against chronic viral hepatitis in human patients. (HEPATOLOGY 2006;44:896–906.)

Interferon type I gene expression in chronic hepatitis C

Hepatitis C virus (HCV) frequently causes chronic liver disease. The cause of viral persistence might be an inappropriate type I interferon (IFN) induction. To analyze the hosts IFN response in chronic hepatitis C, we measured the transcription level of type I IFN genes as well as type I IFN-regulated genes in liver tissue and corresponding blood samples from patients with chronic hepatitis C, nonviral liver diseases, and a suspected but later excluded liver disease. Competitive and real-time RT-PCR assays were used to quantify the messenger RNA (mRNA) levels of all known IFN-α, IFN-β, and IFN-λ genes and those of some IFN-regulated genes. We failed to detect any hepatic type I IFN mRNA induction, although liver tissue of chronic hepatitis C patients contained high numbers of some type I IFN-inducible effector mRNA molecules. Analysis of peripheral blood samples, however, showed a clear type I IFN induction. Parallel experiments employing HCV replicon cell lines revealed that replication of HCV RNA is not sufficient to induce any type I IFN nor to induce directly type I IFN-regulated genes such as MxA. In conclusion, our data provide evidence for the absence of an induction of type I IFN genes by HCV in the human liver and argue for a further development of type I IFN-based therapies.

Endoscopic ultrasound of the colon for the differentiation of Crohn's disease and ulcerative colitis in comparison with healthy controls

Diagnosis of inflammatory bowel disease (IBD) is based on clinical presentation, colonoscopy and histology. Differentiation of Crohns disease (CD) and ulcerative colitis (UC) can be difficult in some patients. Endoscopic ultrasound (EUS) provides high resolution images of the gastrointestinal wall (GI) and may be an alternative to differentiate CD/UC.

Quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy for non-resectable liver metastases of colorectal cancer

Objective Patients with non-resectable liver metastases of colorectal cancer have poor prognosis and are mainly treated by palliative chemotherapy. Laser interstitial thermo-therapy is an innovative minimal invasive procedure for local tumour destruction within solid organs. The aim of the study was to investigate quality of life and outcome of ultrasound-guided laser interstitial thermo-therapy (US-LITT) in patients with liver metastases of colorectal cancer. Methods In this prospective non-randomized study, 45 patients with liver metastases of colorectal cancer were palliatively treated by US-LITT. Patient survival was analysed by the Kaplan–Meier method and the quality of life by questionnaire C30 of the European Organisation for Research and Treatment of Cancer before, and 1 week, 1 month, and 6 months after initiation of US-LITT. Results Median survival after initiation of US-LITT was 8.5 ± 0.7 months with a range of 1.5–18 months. Body weight was constant 1 month after US-LITT. In the multivariate analyses, quality-of-life symptoms and functioning scales did not deteriorate in patients alive at 6 months after initiation of US-LITT. Univariate analyses outlined a significant increase of the pain subscale before and at 1 week after US-LITT. Conclusions This study first describes the quality of life in patients with liver metastases of colorectal cancer treated by US-LITT. Potential benefits of the minimal invasive procedure could be prolonged survival time by preserved quality of life, but this first impression needs to be verified in a comparative study.

Ultrasonographic guided laser-induced interstitial thermotherapy (LITT) of hepatic metastases

Background: In patients with unresectable hepatic metastases or primary liver tumors therapeutic options are limited. Laser-induced thermotherapy could be a minimal invasive option for palliative treatment of hepatic metastasized tumors. Thereby, absorption of laser light energy induces denaturation of proteins and thermocoagulation of tumor cells. Methods: Laser coagulation was performed by using a neodymium-yttrium alum/n/urn garnet (Nd:YAG) laser (Dornier MediLas fibertom 4100) with a scattering-dome light emitter and a water-cooled application catheter (Somatex). On the basis of ex vivo experiments 36 patients with unresectable hepatic tumors (15 colorectal carcinomas, 7 pancreatic adenocarcinomas, 4 gastric carcinomas, 4 metastasized midgut carcinoids, 5 hepatocellular carcinomas, 1 cholangiocellular carcinoma) were treated with LII3. After local anesthesia and intravenous sedation with midazolam laser probes were placed percutaneously under ultrasonographic guidance. Up to 5 metastases were treated per session. Results: During laser light emission uitrasonographic imaging showed a marked signal enhancement that allowed estimation of the coagulation zone. Percutaneous LITT was performed without any side effects such as bleeding, infection or liver injury. The 30 day mortality was zero. Patients left the hospital within 3 days after LITT. A significant tumor reduction was demonstrated by abdominal CT or MRT. Conclusions: It can be concluded that percutaneous LITT can be safely performed under ultrasonngraphic guidance in patients with malignant liver tumors. LITI induces significant destruction of tumor mass as verified by abdominal CT or MRT.