IL-28B polymorphisms and amino acid substitution in the HCV core region predicted SVR to telaprevir, MG-132 molecular weight pegylated interferon, and ribavirin.7 Mehta et al.8 reported an SVR rate of 21% in treated patients in an urban HIV clinic but only 0.7% in the full cohort; the latter was due to a low referral rate. New treatment strategies are needed for HCV-infected and HIV/HCV-coinfected patients in urban settings because of the low rates of SVR, particularly in genotype 1 HIV–infected non-Caucasian men.

If a larger series corroborates these results, maintaining the current standard of care in this subpopulation of HCV-infected individuals should be questioned. Using IL-28B genotyping to assist with treatment decisions and SB203580 deferring therapy until new targeted therapies are available should be considered. Clinicians are faced with the dilemma of recommending immediate treatment or warehousing patients (i.e., foregoing

standard-of-care treatment) in anticipation of novel therapies. Finally, when clinicians discuss the possible benefits and risks of hepatitis C therapy, the sobering, real-world treatment results should be made available to their patients. “
“Dill et al. demonstrated how aberrant activation of Notch2 signaling in albumin-expressing cells of AlbCre/N2ICD mice resulted in hepatocellular carcinomas (HCCs) associated with proliferation and expansion of immature biliary epithelial cells (BECs).[1] HCC formation was enhanced by treatment Rolziracetam with diethylnitrosamine (DEN), which induced the appearance of combined HCC-cholangiocarcinoma (CCC) and of CCC with immature BEC features.[1] Expansion of the BEC compartment in AlbCre/N2ICD mice mimics activation of hepatic stem cells (HpSCs) in human diseases characterized by Notch2 up-regulation.[2] Moreover, aberrant Notch2 signaling induces the formation of human liver cancers with HpSC features.[3] Thus, the HpSC compartment is the most likely candidate for oncogenic events in AlbCre/N2ICD mice, supporting the concept that a spectrum of liver cancers could originate from activation of HpSCs. Alternatively, it was proposed that CCCs might originate

from dedifferentiation of hepatocytes.[4, 5] This provocative assumption is based on observations by genetic tracing studies that CCCs arose from albumin- or transthyretin-expressing cells.[4, 5] However, albumin and transthyretin are expressed in cells undergoing liver differentiation from embryoid bodies[6] and in hepatic and biliary tree stem/progenitors in intrahepatic (canals of Hering) and/or extrahepatic (peribiliary glands) niches.[7, 8] In the studies by Dill et al.,[1] biliary hyperplasia and large biliary cyst formation were induced, even though the albumin gene promoter was targeted to induce selective hepatic N2ICD overexpression. Therefore, albumin-expressing cells in different anatomical sites could have been targeted.