Tumour burden score for hepatocellular carcinoma: Is it an authentic prognostic marker?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163375/2/bjs11927.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163375/1/bjs11927_am.pd

Thrombocytosis is associated with worse survival in patients with hepatocellular carcinoma

Background & AimsThrombocytosis is associated with more aggressive tumour biology in many malignancies. There are limited data in patients with hepatocellular carcinoma (HCC), which often occurs in patients with cirrhosis and portal hypertension. We aimed to explore the prognostic value of thrombocytosis in two cohorts of patients with HCC.MethodsWe included 3561 patients from Taiwan and 1145 patients from the USA. Thrombocytopenia was defined as platelet count < 150à 109/L and thrombocytosis as - ¥Â 300 à  109/L at HCC diagnosis. We used multivariable Cox proportional hazard models to identify independent predictors of survival.ResultsThrombocytosis was present in 9.0% and 6.9% of Taiwan and USA patients respectively. Compared to patients with normal platelet counts and those with thrombocytopenia, patients with thrombocytosis had larger tumours, increased vascular invasion and a higher proportion had extrahepatic metastases in both cohorts. In multivariable analysis, thrombocytosis (aHR 1.40, 95% CI 1.23- 1.60) and thrombocytopenia (aHR 1.13, 95% CI 1.04- 1.23) were both associated with worse survival after adjusting for age, gender, liver disease aetiology, Child- Pugh score, maximal tumour size, tumour nodularity, vascular invasion, lymph node or distant metastasis, performance status and alpha- fetoprotein level. Patients with thrombocytosis had a median survival of 6 and 4 months in the Taiwan and USA cohorts, compared to 32 and 14 months for those with normal platelet counts and 38 and 16 months for thrombocytopenic patients.ConclusionThrombocytosis is independently associated with increased tumour burden and worse overall survival among HCC patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162769/2/liv14560.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162769/1/liv14560_am.pd

Using nomogram of the Barcelona Clinic Liver Cancer system for treatment selection in patients with stage C hepatocellular carcinoma

Abstract Background The nomogram of the Barcelona Clinic Liver Cancer (BCLC) for hepatocellular carcinoma (HCC) has been used for outcome prediction. Patients with BCLC stage C HCC often undergo anti-cancer therapy against current treatment guidelines in real world practice. We aimed to use the nomogram to provide guidance on treatment selection for BCLC stage C patients. Methods A total of 1317 patients with stage C HCC were retrospectively analyzed and divided into four groups by nomogram points. One-to-one matched pairs between patients receiving different treatments were generated by the propensity score with matching model within these groups. Survival analysis was performed by Kaplan-Meier method with log-rank test. Results Patients with higher nomogram points were more often treated with targeted or supportive therapies (p  15, there was no significant difference in survival between patients receiving two different treatment strategies. Conclusions The nomogram of BCLC system is a feasible tool to help stage C HCC patients to select primary anti-cancer treatment in pursuance of better overall survival.https://deepblue.lib.umich.edu/bitstream/2027.42/142787/1/12885_2018_Article_4202.pd

Albuminâ bilirubin gradeâ based nomogram of the BCLC system for personalized prognostic prediction in hepatocellular carcinoma

Background & AimsThe prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. We aimed to develop and validate an albuminâ bilirubin (ALBI) gradeâ based nomogram of BCLC to estimate survival for individual HCC patient.MethodsBetween 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analysed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram.ResultsBeta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3â and 5â year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71â 0.81) in the derivation cohort and 0.76 (95% CI: 0.71â 0.81) in the validation cohort. The calibration plots to predict both 3â and 5â year survival rate well matched with the 45â degree ideal line for both cohorts, except for ALBIâ based BCLC stage 0 in the validation cohort.ConclusionsThe proposed ALBIâ based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and userâ friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/1/liv14249_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153250/2/liv14249.pd

Improvement of Carbon Tetrachloride-Induced Acute Hepatic Failure by Transplantation of Induced Pluripotent Stem Cells without Reprogramming Factor c-Myc

The only curative treatment for hepatic failure is liver transplantation. Unfortunately, this treatment has several major limitations, as for example donor organ shortage. A previous report demonstrated that transplantation of induced pluripotent stem cells without reprogramming factor c-Myc (3-genes iPSCs) attenuates thioacetamide-induced hepatic failure with minimal incidence of tumorigenicity. In this study, we investigated whether 3-genes iPSC transplantation is capable of rescuing carbon tetrachloride (CCl4)-induced fulminant hepatic failure and hepatic encephalopathy in mice. Firstly, we demonstrated that 3-genes iPSCs possess the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that exhibit biological functions and express various hepatic specific markers. 3-genes iPSCs also exhibited several antioxidant enzymes that prevented CCl4-induced reactive oxygen species production and cell death. Intraperitoneal transplantation of either 3-genes iPSCs or 3-genes iPSC-Heps significantly reduced hepatic necrotic areas, improved hepatic functions, and survival rate in CCl4-treated mice. CCl4-induced hepatic encephalopathy was also improved by 3-genes iPSC transplantation. Hoechst staining confirmed the successful engraftment of both 3-genes iPSCs and 3-genes iPSC-Heps, indicating the homing properties of these cells. The most pronounced hepatoprotective effect of iPSCs appeared to originate from the highest antioxidant activity of 3-gene iPSCs among all transplanted cells. In summary, our findings demonstrated that 3-genes iPSCs serve as an available cell source for the treatment of an experimental model of acute liver diseases

Staging and Restaging for Hepatocellular Carcinoma: Solution of Confusion?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146924/1/hep30324.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146924/2/hep30324_am.pd

Model for End-stage Liver Disease and Organ Allocation in Liver Transplantation: Where Are We and Where Should We Go?

The Child-Turcotte-Pugh (CTP) score has been used for decades to measure the severity of chronic liver disease. Recent studies have shown that the model for end-stage liver disease (MELD) more accurately predicts the short-and mid-term survival for patients with cirrhosis compared to the CTP system. MELD, which has 3 parameters (serum bilirubin, creatinine, and prothrombin time) that need logarithmic transformation, has the advantage of a wide-range continuous scale and is more objective and less variable. The liver allocation system has changed from a status-based algorithm using the CTP score, to one using a continuous MELD severity score as a reference system to prioritize adult patients on the waiting list since 2002 in the USA. However, there are potential limitations of MELD. An intrinsic defect is that some important parameters, such as hepatic encephalopathy and ascites, which are common adverse complications in cirrhosis, are not included in MELD. It has been suggested to incorporate a low serum sodium level into the prognostic model to enhance the predictive ability. Moreover, the change of MELD over time may provide updated information for patients on the transplant waiting list. In summary, although there was encouraging evidence supporting the prognostic advantage of MELD, the optimal role of MELD in the setting of outcome assessment for cirrhotic patients needs more study. Appropriate modifications and fine tuning of MELD are necessary for determining the ranking status of patients on the waiting list, to avoid a futile transplantation and improve overall patient survival

Assessing liver dysfunction in cirrhosis: Role of the model for end-stage liver disease and its derived systems

The model for end-stage liver disease (MELD) has replaced the role of the Child–Turcotte–Pugh system as a more commonly used system in evaluating the severity of liver dysfunction in patients with chronic liver disease, owing to its superior ability to predict survival. The United Network of Organ Sharing (UNOS) in the USA has used the MELD system for prioritizing donor grafts in advanced cirrhotic patients awaiting liver transplantation since 2002. Serum sodium level is another important prognostic predictor in cirrhosis. Consequently, by incorporating serum sodium into the original MELD, the MELD-Na, MELDNa, the MELD-to-sodium ratio (MESO) index, and the ReFit MELDNa were proposed in an attempt to improve the predictive ability of the original MELD. Nevertheless, there are some limitations of the MELD-based systems that need to be refined. The MELD-based systems merely use laboratory data as parameters for the equation, therefore, any lack in unification and standardization of laboratory methods will result in inconsistent data that affect the prioritization of liver transplantation. Furthermore, the MELD system includes creatinine as a parameter, and serum creatinine level may represent different degrees of renal dysfunction in men and women. Therefore, these limitations may compromise the fair process of organ allocation for female cirrhotic patients. Currently, the application of the MELD system has been extended to tumor staging of hepatocellular carcinoma. Several studies have replaced the Child–Turcotte–Pugh system with the MELD as a parameter, indicating that the use of different criteria of liver dysfunction in cancer staging may enhance prognostic accuracy. Although the outcome data of the modified staging systems need to be confirmed, the concept of using the MELD as a reference system for evaluating the severity of liver dysfunction has globally become an important issue