Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Elastography as a predictor of liver cirrhosis complications after hepatitis C virus eradication in the era of direct-acting antivirals

Chronic inflammation due to hepatitis C virus(HCV)infection leads to liver fibrosis and rearrangement of liver tissue,which is responsible for the development of portal hypertension(PH)and hepatocellular carcinoma(HCC).The advent of direct-acting antiviral drugs has revolutionized the natural history of HCV infection,providing an overall eradication rate of over 90%.Despite a significant decrease after sustained virological response(SVR),the rate of HCC and liver-related complications is not completely eliminated in patients with advanced liver disease.Although the reasons are still unclear,cirrhosis itself has a residual risk for the development of HCC and other PH-related complications.Ultrasound elastography is a recently developed non-invasive technique for the assessment of liver fibrosis.Following the achievement of SVR,liver stiffness(LS)usually decreases,as a consequence of reduced inflammation and,possibly,fibrosis.Recent studies emphasized the application of LS assessment in the management of patients with SVR in order to define the risk for developing the complications of chronic liver disease(functional decompensation,gastrointestinal bleeding,HCC)and to optimize long-term prognostic outcomes in clinical practice.

Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

Immunotherapy for the treatment of hepatocellular carcinoma: finally in clinical practice

Clinical guidelines for the prevention,diagnosis and management of human disease are evidence-based tools that rely on quality of clinical research,including data from randomized controlled clinical trials(RCTs)and real-world evidence.The Society for Immunotherapy of Cancer(SITC)recently published a clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma(HCC)(1).

Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives

Hepatocarcinogenesis is a multistep process,heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis.Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways.As hepatocellular carcinoma has higher arterial vascularization than normal liver,this could be a good target for novel molecular therapies.Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor.The importance of this drug lies not only in the modest gain of patients' survival,but in having opened a roadmap towards the development of new molecules and targets.Unfortunately,after the introduction of sorafenib,during the last years,a wide number of clinical trials on antiangiogenic therapies failed in achieving significant results.However,many of these trials are still ongoing and promise to improve overall survival and progression-free survival.A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib,thus opening new interesting therapeutic perspectives.Many other expectations have been borne from the discovery of the immune checkpoint blockade,already known in other solid malignancies.Furthermore,a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional support.This review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies,the actual evidence and the future perspectives concerning drug therapy in this open field.