Yet, after Sox9 could be detected in intrahepatic bile ducts at embryonic day 16.5, the source of hepatocyte differentiation switched from Sox9-negative hepatoblasts to the Sox9-positive cells from within the developing biliary tree—the adult

scenario. For those not working in the field in 1985, or indeed some older hepatologists with short memories, Gershom Zajicek published his “streaming liver” hypothesis in that year.22 Basically, it stated that hepatocytes were produced near the portal areas and migrated centripetally toward the hepatic veins where they underwent 5-Fluoracil concentration a cell death process. The hypothesis was based on a pulse-chase analysis made on a group of normal rats injected with the DNA substrate tritiated thymidine; as time progressed the average distance of the labeled hepatocytes from the portal areas increased, hence they “streamed”.

These experiments were often criticized on technical grounds, mainly because tritiated thymidine could be released from dead cells, e.g., bone marrow cells, and then be reused by cells synthesizing DNA at later time points; hence, the experiment was not a true pulse-chase. So, although lacking a little in modern-day sophistication, Zajicek’s hypothesis appears essentially correct, with elegant lineage tracing in the study by Furuyama et al.21 adding the fact that biliary epithelial cells are also the MCE main instigators of physiological liver replacement—in essence, establishing a new paradigm of liver homeostasis. However, it is still unclear, as in oval Belnacasan in vivo cell reactions, if all cells within the intrahepatic biliary tree are potential hepatocyte progenitors, or whether this property is confined to a subpopulation. Only time will tell. “
“A 61-year-old Japanese woman suffered from a small, painful, subcutaneous nodule on the sole of her foot that was 10 mm across in diameter during pegylated interferon (PEG IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C. Skin biopsy revealed multiple non-caseating granulomas composed

of epithelioid histiocytes with multinucleate giant cells, which was consistent with sarcoidosis. Ophthalmologic examination revealed uveitis. Thoracic computed tomography (CT) showed multiple bilateral hilar lymphadenopathies and a diffuse micronodular interstitial pattern of the lungs. Genetic analysis indicated a probable homozygous haplotype of A*02:01-C*15:02-B*51:01-DRB1*16:02-DQB1*05:02 in human leukocyte antigen regions. The patient was observed carefully without any additional medication because no significant systemic symptoms were noted. Combination therapy was continued for 2 months afterwards. She was asymptomatic for over 3 years of follow up, and repeated hematological and biological investigations and chest CT showed improvement.