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Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.
Several studies have shown improved outcome of liver transplant (LT) recipients with hepatitis C virus (HCV) since the widespread clinical use of interferon-free direct-acting antivirals (IFN-free DAAs). However, the association of IFN-free DAA therapy on tumor characteristics and on the outcome of LT in patients with hepatocellular carcinoma (HCC) has not been studied. We aimed to examine pre-transplant HCC characteristics and post-LT outcomes in the IFN-based DAA treatment and IFN-free DAA treatment eras.

Using the United Network for Organ Sharing/Organ Procurement and Transplantation Network database, we analyzed adults with a diagnosis of HCV and HCC who received LTs from deceased donors from 04/2012 to 12/2017. Cox regression models were used to identify the association between the IFN-based DAA treatment vs IFN-free DAA treatment era and study outcomes (mortality, graft failure, and HCC recurrence at 1 and 3 years).

Complete tumor necrosis was significantly higher in the IFN-free DAA treatment eracantly higher complete tumor necrosis in explants. Other HCC tumor characteristics were similar between the two eras. Post-LT graft failure at 1 and 3 years significantly decreased in the IFN-free DAA treatment era among patients with HCV and HCC, although patient mortality was not statistically different.
Cancer stem cells (CSCs) have been considered involving in tumorigenesis, local recurrence, and therapeutic drug resistance of hepatocellular carcinoma (HCC). To investigate novel and effective methods for targeting hepatic CSCs is crucial for a permanent cure of liver cancer.

The expression level of SIRT1 was detected in CSCs of HCC tissues and cancer cell lines. Expression of CSC markers, the self-renewal and tumorigenic ability of liver CSCs were analyzed with SIRT1 inhibition. Cellular senescence-related markers were used to detect CSCs senescence after inhibition of SIRT1.

SIRT1 was highly expressed in CSCs of HCC cell lines and human HCC tissues. In vitro study revealed that decreasing of SIRT1 level significantly downregulated the stemness-associated genes of liver CSCs and reduced the CSC stemness properties. Also, downregulated SIRT1 suppressed liver CSCs proliferation by decreasing their self-renewal abilities. Furthermore, CSCs with decreased SIRT1 expression showed limited tumorigenicity and formed smaller HCC tumor in vivo. And SIRT1 decreased CSCs became more susceptible to chemotherapeutic drugs. Kartogenin research buy Mechanistically, SIRT1 decreased CSCs became senescence through the activation of p53-p21 and p16 pathway. The data further indicated that the tumor formed from SIRT1-knockdown CSCs exhibited higher senescence-associated β-galactosidase (SA-β-Gal) activity but lower proliferative capacity.

Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.
Taken together, these findings pointed that induction of senescence in liver CSCs is an effective tumor suppression method for HCC, and SIRT1 may be served as a promising target for HCC treatment.
Liver imaging reporting and data system (LI-RADS) classification, especially the identification of LR-3 to 5 lesions with hepatocellular carcinoma (HCC) probability, is of great significance to treatment strategy determination. We aimed to develop a semi-automatic LI-RADS grading system on multiphase gadoxetic acid-enhanced MRI using deep convolutional neural networks (CNN).

An internal data set of 439 patients and external data set of 71 patients with suspected HCC were included and underwent gadoxetic acid-enhanced MRI. The expert-guided LI-RADS grading system consisted of four deep 3D CNN models including a tumor segmentation model for automatic diameter estimation and three classification models of LI-RADS major features including arterial phase hyper-enhancement (APHE), washout and enhancing capsule. An end-to-end learning system comprising single deep CNN model that directly classified the LI-RADS grade was developed for comparison.

On internal testing set, the segmentation model reached a mean dining system. This deep learning-based system may improve workflow efficiency for HCC diagnosis in clinical practice.
We developed a semi-automatic step-by-step expert-guided LI-RADS grading system (LR-3 to 5), superior to the conventional end-to-end learning system. This deep learning-based system may improve workflow efficiency for HCC diagnosis in clinical practice.
The importance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in hepatocellular carcinoma (HCC) has been studied extensively in Japan, where hepatitis C virus is the predominant aetiology of HCC. The clinical profiles of HCC regarding the state of AFP and DCP in a hepatitis B virus epidemic area have not been comprehensively investigated, and the value of these tumour markers in evaluating the response to treatment and the detection of recurrence has yet to be determined.

A total of 4792 patients treated in our centre were continuously analysed regarding accessible AFP and DCP data pre- and posttreatment. Baseline characteristics were summarized, and comparisons of progression-free survival (PFS) and overall survival (OS) rates were made independently. The prognostic significance of each factor was tested with the Cox proportional hazards model. Patients who had AFP and DCP data pretreatment, pre- and posttreatment, and those who were continuously monitored more than twice were analysed separately.
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