atp citrate lyase The most important risk factor for

The most important risk factor for HCC is chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (). The risk of HCC is increased 5- to 15-fold in chronic HBV carriers () and 11.5- to 17-fold in HCV-infected patients (). In addition, epidemiological studies have shown that chronic inflammation of the liver predisposes individuals to HCC. Cirrhosis is an additional risk factor for HCC; the annual risk of HCC is between 1% and 6%. HBV and HCV infections are now treatable diseases. After a decade of using PEG2a/RBV to treat chronic hepatitis C patients, telaprevir and simeprevir, NS3/4A protease inhibitors, co-administered with PEG2a/RBV were approved for HCV atp citrate lyase 1 infected patients and demonstrating significant improvements in sustained virological response (SVR) rates (). Recently, asunaprevir and daclatasvir represent the first all oral, interferon free direct-acting anti viral agents (DAA) containing regimen and are approved for treating patients with HCV genotype 1 infections. These drugs demonstrate significant improvements in SVR rates without interferon related side-effects. Likewise, nucleoside analogues are recognized as more effective agents for chronic hepatitis B patients compared with that of interferon therapy. Lamivudine, adefovir (in 2002), entecavir (in 2005), telbivudine (in 2006), and tenofovir disoproxil fumarate (in 2008) have been licensed. These nucleoside analogues suppress HBV replication through inhibition of reverse transcriptase and DNA polymerase, and inhibit reverse transcription of pregenomic RNA to HBV DNA. Previous studies have shown that successful anti-viral therapy can improve biochemical liver function parameters as well as histological findings (). Patients with mild liver fibrosis are likely to show histologically evident decreases in fibrosis and inflammation after a SVR in response to IFN treatment against HCV infection (). Furthermore, treated patients show marked reductions in decompensated liver disease and HCC occurrence (). Patients with advanced fibrosis, however, retain relatively low but still considerable risks of HCC occurrence despite having attained SVR (). Risk of HCC development increases in proportion to the degree of liver fibrosis in patients persistently infected with hepatitis virus. Anti-viral therapy has been shown to decrease the risk of hepatic decompensation () and HCC occurrence () among sustained virologic responders. In chronic HCV infected patients, prevention of unfavorable disease outcome seems most effective when therapy is given before development of cirrhosis (). On the other hand, oral nucleoside analogues are beneficial for patients with even decompensated HBV-related cirrhosis and HCC (). Improvement of anti-viral therapy will decrease the incidence of HCC. However, surveillances to detect HCC at an early stage are still indispensable to those who achieved SVR. Serum autoantibodies to TAA can be used as a new predictive biomarker for early assessment of HCC. Disclosure
The accumulating data from randomized clinical trials provide the rational to consider the potential role of daily aspirin use in colorectal cancer (CRC) prevention, and possibly other types of cancer (). However, some questions require to be addressed before the recommendation for the prophylactic use of aspirin in the population: (i) what is the mechanism of the anti-tumorigenic effect of aspirin?; (ii) is the chemopreventive effect dose-dependent?; (iii) may daily low-dose aspirin affect other types of cancers in addition to CRC?; (iv) does the reduced risk of colorectal cancer by daily aspirin outweigh harm from aspirin-induced bleeding? In this issue of , provide novel insights into the mechanism of action of aspirin in preventing CRC. They addressed the hypothesis that the drug normalizes the expression of epidermal growth factor receptor (EGFR), a transmembrane receptor tyrosine kinase of the ErbB family implicated in the etiology of CRC (). Moreover, they explored the possibility that the effect of aspirin was dependent on its capacity to modulate cyclooxygenase (COX)-2 expression. The COX enzyme catalyzes the rate-limiting oxidative and peroxidative enzymatic steps in the biosynthesis of prostanoids which affect colorectal tumorigenesis a number of distinct mechanisms (). They studied the expression levels of colonic EGFR and COX-2, in familial adenomatous polyposis (FAP) patients, sub-grouped on pathological disease stage, normal individuals. They found that EGFR and COX-2 proteins were overexpressed as compared to controls in premalignant and malignant lesions and that the two proteins were colocalized. Mechanistic studies performed in human colonic epithelial cells as well as in murine embryonic fibroblasts clearly showed that COX-2 overexpression triggers the activation of the c-Jun-dependent transcription factor, activator protein-1 (AP-1), which binds to the promoter, thus leading to EGFR accumulation. Interestingly, they found that FAP patients who were classified as regular aspirin users [if they reported taking two or more standard (325mg) aspirin tablets per week within the previous 12months] showed lower levels of EGFR and also COX-2.