Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

BACKGROUND At the diagnosis of hepatocellular carcinoma(HCC),more than 90%of HCC patients present cirrhosis,a clinical condition often associated to malnutrition.Sarcopenia is an indirect marker of malnutrition assessable on computed tomography(CT).AIM To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial(chemo)-embolization.METHODS Patients with HCC treated by a first session of trans-arterial(chemo)embolization and an available CT scan before treatment were included.Sarcopenia was assessed using skeletal muscle index at baseline and at the first radiological assessment.Radiological response was recorded after the first session of treatment using mRECIST.RESULTS Of 225 patients treated by trans-arterial bland embolization(n=71)or trans-arterial chemoembolization(n=154)for HCC between 2007 and 2013,Barcelona Clinic of Liver Cancer stage was A,B,and C in 27.5%,55%,and 16.8%of cases,respectively.Sarcopenia was present in 57.7%of the patients.Patients with sarcopenia presented a higher rate of progressive disease(19%vs 8%,P=0.0236),a shorter progression-free survival(8.3 vs 13.2 mo,P=0.0035),and a shorter median overall survival(19.4 mo vs 35.5 mo,P=0.0149)compared with non-sarcopenic patients.Finally,patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis(P=0.0004).CONCLUSION Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial(chemo)-embolization for HCC.

Next generation sequencing, inter-tumor heterogeneity and prognosis of hepatitis B related hepatocellular carcinoma

Hepatocellular carcinoma（HCC）is one of the leading causes of cancer related death in Asia and Africa（1）.It reflects the high burden of hepatitis B virus（HBV）infection in these areas.Curative treatments of HCC as radiofrequency ablation and resection are impaired by a high rate of tumor recurrence.However,most of the time,HCC is frequently diagnosed at advanced stages where only

Molecular Determinants of Prognosis in Hepatocellular Carcinoma

Hepatocellular carcinoma is one of the leading causes of death by cancer worldwide.Prognosis of hepatocellular carcinoma is determined by characteristics of the tumor and the surrounding cirrhotic liver.Several molecular signatures reflecting tumor biology and derived from tumor analyses predict early tumor recurrence and survival.In contrast,molecular signatures from cirrhotic non-tumor samples are enriched in immunity/inflammation related genes and could predict late tumor recurrence.Moreover,combination of clinical,pathological,and molecular features may refine prognosis prediction in these patients.Finally,molecular signatures from both tumor and non-tumor tissues will be helpful in the future to guide treatments in different clinical settings.

Systemic treatment of hepatocellular carcinoma:the times they are a-changin’

For a decade,sorafenib remained the only drug approved for the treatment of advanced hepatocellular carcinoma(HCC)due to the failure of several phase III trials in which alternative angiogenesis inhibitors were tested(1).In recent years,the field of systemic treatments of HCC has evolved quickly and a recent position paper of the European Association for the Study of the Liver has well described the current advances in the systemic treatment of advanced HCC as well as the unmet needs in the field(1).First,lenvatinib was approved as an alternative to sorafenib in the first-line setting,and,thus,regorafenib,cabozantinib and ramucirumab as second-line treatments for patients who progressed on sorafenib(1).

Molecular mechanisms of liver carcinogenesis related to metabolic syndrome

Global prevalence of non-alcoholic fatty liver disease(NAFLD)and of NAFLD-hepatocellular carcinoma(HCC)is estimated to grow in the next years.The burden of NAFLD and the evidence that NAFLD-HCC arises also in noncirrhotic patients,explain the urgent need of a better characterization of the molecular mechanisms involved in NAFLD progression.Obesity and diabetes cause a chronic inflammatory state which favors changes in serum cytokines and adipokines,an increase in oxidative stress,DNA damage,and the activation of multiple signaling pathways involved in cell proliferation.Moreover,a role in promoting NAFLD-HCC has been highlighted in the innate and adaptive immune system,dysbiosis,and alterations in bile acids metabolism.Several dietary,genetic,or combined mouse models have been used to study nonalcoholic steatohepatitis(NASH)development and its progression to HCC,but models that fully recapitulate the biological and prognostic features of human NASH are still lacking.In humans,four single nucleotide polymorphisms(PNPLA3,TM6SF2,GCKR,and MBOAT7)have been linked to the development of both NASH and HCC in cirrhotic and non-cirrhotic patients,whereas HSD17B13 polymorphism has a protective effect.In addition,higher rates of somatic ACVR2A mutations and a novel mutational signature have been recently discovered in NASH-HCC patients.The knowledge of the molecular pathogenesis of NAFLD-HCC will be helpful to personalized screening programs and allow for primary and secondary chemopreventive treatments for NAFLD patients who are more likely to progress to HCC.

Percutaneous ablation for HCC eligible to transplantation: providing more opportunities of remission in the context of graft shortage

Liver transplantation(LT)is still considered as the best treatment for small HCC as compared to other curative therapeutic options such as resection and ablation,at least in theory.Recently Lee et al.(1)reported an excellent 10 years intention to treat overall survival in patients with HCC within Milan criteria after first line radiofrequency ablation followed by LT and challenged the alarming study of Llovet et al.