While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 Ϯ 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age Ն50 yr, JEI Ͼ7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time Ն35 seconds, and creatinine Ն1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of Ն33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. See Editorial on Page 786Fulminant hepatic failure (FHF) is a complex multisystem illness that results after a catastrophic insult to the liver, manifesting in the development of a coagulopathy and encephalopathy within a short period of time.1 It carries high mortality rate with short-term transplantfree survival rate of 43%.2 Moreover, it accounts for about 7% of liver transplants among adults.3 Therefore, the determination of prognosis for accurately predicting the outcome in FHF is of immense value in establishing Abbreviations: KCH, King's College Hospital; MELD, Model for End-Stage Liver Disease; LT, liver transplantation; CPI, clinical prognostic indicators; FHF, fulminant hepatic failure; JEI, jaundice-encephalopathy interval; ROC, receiver operating characteristic curves; PPV, positive predictive value; NPV, negative predictive value; IgM, immunoglobulin M.

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Progression of liver fibrosis to HCC (hepatocellular carcinoma) is a very complex process which involves several pathological phenomena, including hepatic stellate cell activation, inflammation, fibrosis and angiogenesis. Therefore inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor everolimus to observe its effect on the in vitro activation of hepatic stellate cells and angiogenesis. The results of the present study demonstrated that everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cell line LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate the activation of primary stellate cells to their activated form. Angiogenesis studies showed that everolimus blocked angiogenesis in a rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.