0000000000121367
AUTHOR
M. Schuchmann
Medikamentöse Schädigung der Leber mit autoimmunem Phänotyp durch TNF-Blockade – Fallvorstellung und Review der Literatur
Die Zulassung von Medikamenten, die die biologische Wirkung von Tumor-Nekrose-Faktor alpha (TNF-α) blockieren, hat die Behandlungsmoglichkeiten von Patienten mit einer Reihe von autoimmun-vermittelten Erkrankungen stark verbessert. Als haufige Nebenwirkung kommt es zu einer gesteigerten Anfalligkeit gegenuber Infekten. Selten treten auch hepatische Nebenwirkungen unter TNF-Blockade auf. Diese reichen von einer moderaten Leberwert- und Bilirubinerhohung uber die Reaktivierung von chronischen Viruserkrankungen, konnen aber auch zum akuten Leberversagen fuhren. In einem Teil der Falle wurde ein autoimmunes Schadigungsmuster mit dem Auftreten von Autoantikorpern und entsprechenden typischen his…
Acute renal failure and liver dysfunction after subcutaneous injection of 3-sn-phosphatidylcholine (Lipostabil®)-case report.
INTRODUCTION Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often caused by drugs especially antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced liver dysfunction and renal failure after subcutaneous injection of phosphatidylcholine was not reported so far. 3-sn-Phosphatidylcholine has been described as a cell lysis reaction-inducing drug. Its in vitro data indicated a relevant toxicity potential. In particular human cell types such as fibroblast-like preadipocytes, vascular and skeletal muscle cells, or renal epithelial cells react more sensitive than other human cell types. CASE REPORT We present a 28-year-old woman who received 3.5…
Control Of Organ Transplant-Associated Graft-versus-Host Disease By Activated Host Lymphocyte Infusions
Background Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal. Methods Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]). Results Adoptive trans…
Transarterial Chemoembolization Before Liver Transplantation in 60 Patients With Hepatocellular Carcinoma
Tumor recurrence is a major problem after orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). In 60 patients OLT was performed for HCC after pretreatment by repeated transarterial chemoembolization (TACE). Forty-four recipients exceeded the Milan criteria. Recurrence-free 5-year survival was 65.2% and 5-year freedom from recurrence was 73.2%. During the waiting time, 14 patients experienced minimal change, which did not fulfill the definition of tumor progression according to official oncological criteria. Five-year freedom from recurrence among patients with stable compared with progressive disease was 93.3% versus 28.1%, respectively (P = .0001). A stri…
Transarterielle Chemoembolisation (TACE) des Hepatozellulären Karzinoms (HCC) bei Patienten mit Pfortaderthrombose - Erfahrungen
PURPOSE: Comparative analysis of the course of disease in patients with initial diagnosis of portal vein thrombosis in HCC treated with sequential TACE. Evaluation of the efficacy and safety of the method in a selected patient cohort. PATIENTS AND METHODS: The study included 22 patients with HCC that were palliatively treated at least 3 times with TACE. All patients presented a portal vein thrombosis in the initial CT investigation. The TACE-procedure was carried out in regular intervals using a suspension consisting of a fixed dosage of Mitomycin C (10 mg) and 10-20 ml Lipiodol. Follow-up investigations were carried out with contrast enhanced Multislice-CT before and after TACE and control…
Hepatitis B virus-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment.
The effect of pegylated interferon-α (IFN) add-on therapy on HBV-specific T-cell responses was evaluated in 12 patients with stable, undetectable hepatitis B virus (HBV) load under nucleos(t)ide analogue therapy. Peripheral blood mononuclear cells were isolated at week 0, 4, 8, 12, 24 and 48 of IFN add-on therapy. Quantity and quality of circulating HBV S- and core-specific CD4 and CD8 T cells were analysed ex vivo by flow cytometry. HBV S- and core-specific CD4 T-cell numbers modestly increased within 8 weeks of IFN administration (P = 0.0391 and P = 0.0195), whereas HBV-specific CD8 T cells in general showed only minor changes under IFN add-on therapy. Functionality of HBV-specific CD4 bu…
Risk Factors in Patients With Rapid Recurrent Hepatitis C Virus–Related Cirrhosis Within 1 Year After Liver Transplantation
Abstract Background Recurrent cirrhosis (RC) due to pretransplant underlying disease leads to organ failure and subsequent death after orthotopic liver transplantation (OLT). RC occurs in up to 30% of patients with recurrent hepatitis C (HCV) within 5 years after OLT. We sought to identify early risk factors for rapid RC within the first year after OLT in HCV-positive patients. Methods Among 404 liver transplanted patients at the University of Mainz between 1998 and 2008, 90 were HCV-RNA positive. To identify predictive factors for rapid RC, we compared HCV-positive patients with advanced fibrosis stages within 1 year after OLT ( n = 13) with these without RC at 5 years after OLT ( n = 23).…
Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95-and TRAIL receptor-mediated apoptosis and chemotherapy
Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased…
Transarterial Chemoembolization in Patients Not Eligible for Liver Transplantation: Single-Center Results
OBJECTIVE. The purpose of this study was to evaluate the effectiveness of transarterial chemoembolization in the care of patients not eligible for liver transplantation.CONCLUSIONS. Prognosis depends on local response, Okuda score, α-fetoprotein level, and tumor size and is independent of the presence of portal venous thrombosis.
285 DOWNREGULATION OF ORGANIC CATION TRANSPORTERS OCT1 (SLC22A1) AND OCT3 (SLC22A3) IN HUMAN HEPATOCELLULAR CARCINOMA AND THEIR PROGNOSTIC SIGNIFICANCE
Background Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).
Sequentielle transarterielle Chemoembolisation (TACE) des hepatozellulären Karzinoms (HCC) - Erfahrungsbericht eines einzelnen Zentrums über 5 Jahre
PURPOSE: To analyze the course of disease of patients treated with sequential TACE and to evaluate the dependent and independent prognostic factors for patient survival using the Cox Proportional Hazard Model. MATERIALS AND METHODS: 94 patients palliatively treated with TACE. Patients were selected if they had been treated at least 3 times. The TACE procedure was carried out at 8-week intervals using a suspension consisting of a fixed dosage of Mitomycin C (10 mg) and 10 ml Lipiodol. Follow-up investigations included contrast-enhanced multislice CT before and after TACE and assessment of the laboratory test results (i. e., blood count, liver enzymes, and coagulation). RESULTS: In 66.7 % of …
The Programmed Death (PD)‐1/PD‐Ligand 1 Pathway Regulates Graft‐Versus‐Host‐Reactive CD8 T Cells After Liver Transplantation
Acute graft-versus-host disease (aGVHD) is a life-threatening complication after solid-organ transplantation, which is mediated by host-reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow-infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host-versus-donor reactivity was selectively impaired, as anti-third-party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor-specific allotol…
Acute organ failure following the loss of anti-apoptotic cellular FLICE-inhibitory protein involves activation of innate immune receptors
Apoptosis signaling is involved in both physiological tissue homeostasis and acute and chronic diseases. The role of regulatory apoptosis signaling molecules and their organ-specific functions are less defined. Therefore, we investigated the loss of the anti-apoptotic cellular FLICE-inhibitory protein (cFLIP) and the mechanisms of the resulting lethal organ failure in vivo using inducible knockout mice. These were generated by crossing floxed cFLIP mice to a tamoxifen inducible Rosa26-creERT2 mouse strain. Death following global loss of cFLIP resulted from liver failure, accumulation of M1-polarized macrophages and accompanying hepatic cell death and inflammation. Apoptosis was also promine…
Klatskin Tumour: Meticulous Preoperative Work-Up and Resection Rate
BACKGROUND: Surgery represents the only potentially curative treatment of hilar cholangiocarcinoma (hilCC). It may be suggested that meticulous preoperative work-up in Asian countries leads to higher resection rates. METHOD: One hundred and eighty-two patients treated in our department between 1998 and 2008 were included in an analysis based on our prospectively recorded database. Among them, 75 % had a percutaneous transhepatic cholangiography as part of their diagnostic work-up. A total of 160 patients underwent explorative surgery and 123 patients were resected (77 % of patients undergoing exploration, 68 % of all patients). RESULTS: Ninety-one percent of the patients were diagnosed to h…
Tacrolimus Monotherapy Without Steroids After Liver Transplantation – A Prospective Randomized Double-Blinded Placebo-Controlled Trial
Early steroid withdrawal after liver transplantation (LT) is desirable in order to reduce steroid side effects. Between February 2000 and August 2004, 110 patients after LT were included in this prospective, randomized, double-blind, placebo-controlled trial. Randomization was performed before LT. In all patients, tacrolimus was used without induction therapy. All patients received methylprednisolon for 14 days, thereafter a double-blinded medication containing either placebo (n = 56) or methylprednisolon (n = 54) for 6 months, which was completely stopped thereafter. End points were patient and graft survival, acute and chronic rejection, and incidence of steroid side effects during the fi…