Hans L. Tillmann

Bio: Hans L. Tillmann is an academic researcher from Veterans Health Administration. The author has contributed to research in topics: Hepatitis B & Hepatitis C. The author has an hindex of 54, co-authored 224 publications receiving 11220 citations. Previous affiliations of Hans L. Tillmann include Durham University & Vidant Medical Center.

Telbivudine versus lamivudine in patients with chronic hepatitis B.

Abstract: To the Editor: We would like to raise four points with respect to the report by Lai et al. (Dec. 20, 2007, issue)1 on the 1-year results of their study comparing telbivudine with lamivudine in patients with hepatitis B virus (HBV) infection. First, the authors elucidate the role of the viral load at week 24 as a predictor for response and resistance. A decrease in the HBV viral load below 1000 copies per milliliter at week 12 has been reported to correlate with response and absence of resistance.2 More recently, a “week-4 prediction” was suggested for a viral-load decrease below 4 log10 copies per milliliter.3 Does this hold true for lamivudine and telbivudine in the study by Lai et al.? Second, telbivudine seems to select the M204I mutations only. M204V, frequently selected with lamivudine therapy, seems to be required for resistance to entecavir; full sensitivity to entecavir is retained with M204I in vitro.4 If these findings are confirmed, sequential telbivudine–entecavir might be an important therapeutic option, whereas sequential lamivudine–entecavir has been associated with an increased rate of resistance.5 Third, have the authors determined whether the HBV genotype plays a role in determining the path of resistance development? Finally, do the mutations found alter the hepatitis B surface antigen (HbsAg) protein sequence? Hans L. Tillmann, M.D. John G. McHutchison, M.D.

Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis

Abstract: Telomere shortening limits the number of cell divisions of primary human cells and might affect the regenerative capacity of organ systems during aging and chronic disease. To test whether the telomere hypothesis applies to human cirrhosis, the telomere length was monitored in cirrhosis induced by a broad variety of different etiologies. Telomeres were significantly shorter in cirrhosis compared with noncirrhotic samples independent of the primary etiology and independent of the age of the patients. Quantitative fluorescence in situ hybridization showed that telomere shortening was restricted to hepatocytes whereas lymphocytes and stellate cells in areas of fibrosis had significantly longer telomere reserves. Hepatocyte-specific telomere shortening correlated with senescence-associated β-galactosidase staining in 84% of the cirrhosis samples, specifically in hepatocytes, but not in stellate cells or lymphocytes. Hepatocyte telomere shortening and senescence correlated with progression of fibrosis in cirrh...

Caspase 8 small interfering RNA prevents acute liver failure in mice.

Abstract: A major concern in therapy of acute liver failure is protection of hepatocytes to prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells. To evaluate the therapeutic efficacy of siRNA in vivo we used different mouse models of acute liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA results in inhibition of caspase 8 gene expression in the liver, thereby preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8 siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95) antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a clinical situation the siRNAs most likely would be applied after the onset of acute liver failure. Therefore we injected caspase 8 siRNA at a time point during AdFasL- and adenovirus wild type (Adwt)-mediated liver failure with already elevated liver transaminases. Improvement of survival due to RNA interference was significant even when caspase 8 siRNA was applied during ongoing acute liver failure. In addition, it is of particular interest that caspase 8 siRNA treatment was successful not only in acute liver failure mediated by specific Fas agonistic agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which is an animal model reflecting multiple molecular mechanisms involved in human acute viral hepatitis. Consequently, our data raise hope for future successful application of siRNA in patients with acute liver failure.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver

Abstract: The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cell's functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease.