The differential diagnosis can include drug-induced cholestasis, cardiac failure and various viral and fungal hepatic infections. With Doppler ultrasonography,

findings consistent with sinusoidal obstruction syndrome are retrograde portal venous flow, a reduction in hepatic venous flow and edema of the gallbladder wall. Treatment with defibrotide may be helpful for some patients but the drug has not been tested in a controlled trial. Ursodeoxycholic acid may also be helpful for prophylaxis in higher-risk patients. Although sinusoidal obstruction syndrome can resolve spontaneously, patients with severe disease can progress to multiorgan failure and death. In the setting of myeloablative regimens, mortality rates are often of the order MK-1775 datasheet of 15–20%. Contributed by “
“Apoptosis (a crucial physiological form of programmed cell death) of hepatocytes

is a critical prerequisite to preserve liver homeostasis and protect against malignant transformation and carcinogenesis. In a report by Weber et al. in this issue of HEPATOLOGY,1 the authors identify the prosurvival B cell lymphoma-2 (Bcl-2) family member myeloid cell leukemia-1 (Mcl-1) as a critical Ridaforolimus cost player in hepatocyte apoptosis. Interestingly, the authors provide data that the increased spontaneous apoptosis observed in hepatocytes lacking Mcl-1 translates into development of malignant hepatocellular carcinoma (HCC)-like lesions in mice starting from 8 months of age. Using a mouse model harboring the loxP-targeted allele of Mcl-1 in addition to Cre recombinase expressed under the albumin promoter, the study provides convincing, genetically precise experimentation and an intriguing finding: increased apoptosis in hepatocytes goes hand in hand with carcinogenesis illustrating an intriguing connection between apoptosis and cancer research. Bcl-2, B cell lymphoma-2; medchemexpress BH3, Bcl-2 homology domain 3; Bid, BH3-interacting domain death agonist; HCC, hepatocellular carcinoma; Mcl-1,

myeloid cell leukemia-1. The critical role of the prosurvival Bcl-2 family members Mcl-1 and Bcl-x(L) in guarding apoptosis in hepatocytes has previously been described by the same group and others.2-4 Mice lacking either Mcl-1 or Bcl-x(L) (both constitutively expressed in the liver) specifically in their hepatocytes present with strongly increased spontaneous hepatocyte apoptosis and liver fibrosis. Furthermore, Mcl-1–deficient hepatocytes are more susceptible to Fas-mediated liver damage.2 Mcl-1 and Bcl-x(L) cooperatively regulate hepatocyte integrity to a point where liver-specific deletion of both proteins leads to rapid postnatal death of experimental animals due to hepatic failure.3 The findings on the apoptotic function of Mcl-1 and Bcl-x(L) are interesting, but somewhat expected, especially in the light of their known antiapoptotic function and their expression pattern in the liver.