Occurrence of Hepatocellular Carcinoma in Patients with Chronic hepatitis C Treated with Direct-Acting Antiviral Therapy

Poznato je kako oboljeli od kronične bolesti jetre učestalije obolijevaju od hepatocelularnog karcinoma. Premda se RNA molekula hepatitis C virusa uspješno eliminira iz cirkulacije direktnodjelujućim antivirusnim lijekovima, HCV RNA može ostati i dalje prisutna u jetrenom tkivu ili perifernim mononuklearnim stanicama te je taj entitet poznat kao okultni HCV. Postoje brojne nedoumice povezane s ponovnom pojavom HCC-a nakon provedenog liječenja DAA terapijom jetrenih stanica kronično zaraženih HCV-om, a jedan od glavnih čimbenika rizika koji dovodi do de novo HCC-a je pojava kroničnosti HCV-a u stanicama jetre. Mnoge studije provedene su s ciljem istraživanja promjena jetrenih stanica inficiranih HCV-om u HCC. Međutim, još uvijek nisu u potpunosti jasni molekularni mehanizmi koji vode do progresije kronične HCV infekcije u HCC i učinak HCV-a na promjenu DNA ploidnosti, što dovodi do ponovnog povratka HCC-a nakon liječenja DAA terapijom. Stoga je cilj ovoga članka razmotriti čimbenike rizika koji bi mogli dovesti do razvoja HCC-a nakon liječenja HCV-a upotrebom DAA terapije, poput uloge ciroze jetre, promjene DNA ploidnosti, reaktivacije virusa hepatitisa B, kao i okultne HCV infekcije.Patients with chronic liver disease are known to be more likely to develop hepatocellular carcinoma (HCC). Although direct-acting antivirals have proven successful in eliminating the hepatitis C virus RNA from blood circulation, the HCV RNA can still remain present in liver tissue or peripheral blood mononuclear cells – a condition known as occult HCV infection. There have been numerous concerns related to the recurrence of HCC after DAA treatment of hepatocytes infected with chronic HCV. One of the major risk factors leading to de novo HCC is the chronicity of HCV in liver cells. Moreover, numerous studies investigated the change of HCV-infected hepatocytes into HCC. However, the molecular mechanisms leading to the progression of chronic HCV infection into HCC, as well as the effect of HCV on the alteration of DNA ploidy that leads to recurrence of HCC after DAA treatment, are still unclear. Therefore, this article examines the risk factors that could lead to the development of HCC after treatment of HCV with DAAs, such as the role of liver cirrhosis, reactivation of hepatitis B virus, alteration of DNA ploidy and occult HCV infection