Biomedical subjects

Perdita Wietzke-Braun

Publications and source records attributed to Perdita Wietzke-Braun.

8 recordsLinked to original sources

PubMed2006

Adult-to-adult right lobe living donor liver transplantation: comparison of endoscopic retrograde cholangiography with standard T2-weighted magnetic resonance cholangiography for evaluation of donor biliary anatomy.

AIM: To compare the value of endoscopic retrograde cholangiography (ERC) and standard T2-weighted magnetic resonance cholangiography (MRC) in the evaluation process as adult-to-adult right lobe living donor liver transplantation (LDLTx) demands a successful outcome, and exact knowledge of the biliary tree is implicated to avoid biliary complications, postoperatively. METHODS: After starting the LDLTx program, 18 liver transplant candidates were selected for LDLTx by a stepwise evaluation process. ERC and standard T2-weighted MRC were performed to evaluate the biliary system of the donor liver. The anatomical findings of ERC and MRC mapping were compared using the Ohkubo classification. RESULTS: ERC allowed mapping of the whole biliary system in 15/15 (100%) cases, including 14/15 (93.3%) with biliary variants while routine MRC was only accurate in 2/13 (15.4%) cases. MRC was limited in depicting the biliary system proximal of the hepatic bifurcation. Postoperative biliary complications occurred in 2 donors and 8 recipients. Biliary complications were associated with Ohkubo type C, E or G in 6/8 recipients, and 2/3 recipients with biliary leak received a graft with multiple (>=2) bile ducts. CONCLUSION: Pretransplant ERC is safe and superior over standard MRC for detection of biliary variations that occur with a high frequency. However, precise knowledge of biliary variants did not reduce the incidence of postoperative biliary complications.

Adult↗

PubMed2006

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-alpha. 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-alpha 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-alpha 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.

Animals↗

PubMed2006

Interferon regulatory factor-1 promoter polymorphism and the outcome of hepatitis C virus infection.

OBJECTIVE: Interferon-alpha (IFN-alpha), an important mediator for the host's innate antiviral defense system, has been approved for the treatment of persistent viral infections. We investigated whether two functional polymorphisms in genes involved in IFN-alpha signaling and effector functions are associated with the natural outcome of hepatitis C virus (HCV) infection and the responsiveness of chronic hepatitis C patients to IFN-alpha therapy. METHODS: Forty-four individuals who had resolved HCV infection spontaneously and 147 patients who developed chronic hepatitis C were analyzed for functional single nucleotide polymorphisms in the promoter regions of the interferon regulatory factor-1 (IRF-1) and myxovirus resistance protein-1 (MxA) genes at positions -300 and -88, respectively. RESULTS: With regard to -300 IRF-1 or -88 MxA genotype distributions or minor allele frequencies, individuals who spontaneously resolved the infection displayed no significant difference compared with those with chronic infections. Among patients with chronic infections, however, the -300AA IRF-1 genotype, associated with a higher IRF-1 transcriptional activity, was absent in patients with chronic HCV genotype 3a infections, with one exception. In contrast to expectations, -300AA IRF-1 individuals with HCV genotype 3a infection were not represented in higher numbers among those with self-limited infections. Regarding IFN-alpha therapy, -300AA IRF-1 chronic hepatitis C genotype 1 patients tend to respond more often than those with the other IRF-1 genotypes. CONCLUSION: Our findings suggest the possibility that the -300AA IRF-1 genotype is associated with outcome in patients with HCV genotype 3 infection. In addition, in HCV genotype-1-infected patients, this genotype appears associated with response to therapy.

Adult↗

PubMed2005

Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients.

AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus (HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time, higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C. METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT). Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received low-dose ribavirin (10 mg(kg/d)) additionally. RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3 showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed (33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response (SVR) rate of only 11.8% (n = 4) could be achieved. CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment without ribavirin, if initial virological response develops early. This finding is worth to be confirmed in a prospective randomized study with pegylated IFN.

Adult↗

PubMed2004

Initial steroid-free immunosuppression after liver transplantation in recipients with hepatitis C virus related cirrhosis.

AIM: Steroids can increase hepatitis C virus (HCV) replication. After liver transplantation (LTx), steroids are commonly used for immunosuppression and acute rejection is usually treated by high steroid dosages. Steroids can worsen the outcome of recurrent HCV infection. Therefore, we evaluated the outcome of HCV infected liver recipients receiving initial steroid-free immunosuppression. METHODS: Thirty patients undergoing LTx received initial steroid-free immunosuppression. Indication for LTx included 7 patients with HCV related cirrhosis. Initial immunosuppression consisted of tacrolimus 2X0.05 mg/kg.d po and mycophenolate mofetil (MMF) 2X15 mg/kg.d po. The tacrolimus dosage was adjusted to trough levels in the target range of 10-15 microg/L during the first 3 mo and 5-10 microg/L thereafter. Manifestations of acute rejection were verified histologically. RESULTS: Patient and graft survival of 30 patients receiving initial steroid-free immunosuppression was 86% and 83% at 1 and 2 years. Acute rejection occurred in 8/30 patients, including 1 HCV infected recipient. All HCV-infected patients had HCV genotype II (1b). HCV seropositivity occurred within the first 4 mo after LTx. The virus load was not remarkably increased during the first year after LTx. Histologically, grafts had no severe recurrent hepatitis. CONCLUSION: From our experience, initial steroid-free immunosuppression does not increase the risk of acute rejection in HCV infected liver recipients. Furthermore, none of the HCV infected patients developed serious chronic liver diseases. It suggests that it may be beneficial to avoid steroids in this particular group of patients after LTx.

Adult↗

PubMed2004

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 host's 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-alpha, IFN-beta, and IFN-lambda 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.

Adolescent↗

PubMed2004

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.

Adult↗

PubMed2003

Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection?

AIM: To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients. METHODS: In this retrospective study, diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection. The presence or absence of cirrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens. Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients. RESULTS: Laparoscopically, cirrhosis was seen in 29.2 % (21/72) and non-cirrhosis in 70.8 % (51/72) of patients. Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients. Laboratory parameters (AST, y-GT, y-globulin fraction) were measured significantly higher as well as significantly lower (prothrombin index, platelet count) in cirrhotic patients than in non-cirrhotic patients. Histologically, cirrhosis was confirmed in 11.1 % (8/72) and non cirrhosis in 88.9 % (64/72). Patients with macroscopically confirmed cirrhosis (n=21) showed histologically cirrhosis in 38.1 % (8/21) and histologically non-cirrhosis in 61.9 % (13/21). In contrast, patients with macroscopically non-cirrhosis (n=51) showed histologically non cirrhosis in all cases (51/51). Thirty-nine of 72 patients were treated with interferon-alfa, resulting in 35.9 % (14/39) patients with sustained response and 64.1 % (25/39) with non response. Non-responders showed significantly more macroscopically cirrhosis than sustained responders. In contrast, there were no significant histological differences between non-responders and sustained responders. CONCLUSION: Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection. Liver biopsy is the best way to assess inflammatory grade and fibrotic stage. The invasive marker for staging, prognosis and management, and treatment outcome of chronic HCV-infected patients need further research and clinical trials. Laparoscopy should be performed for recognition of cirrhosis if this parameter is found to be of prognostic and therapeutic relevance in patients with chronic HCV infection.

Adult↗