Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus:Current Status and Controversy

The proportions of patients with hepatocellular carcinoma(HCC)involving portal vein tumor thrombus(PVTT)varies greatly in different countries or regions,ranging from 13%to 45%.The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly.In recent years,with the progress and development of surgical concepts,radiotherapy techniques,systematic therapies(for example,VEGF inhibitors,tyrosine kinase inhibitors and immune checkpoint inhibitors),patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved.To achieve the maximum benefit,both clinicians and patients need to think rationally about the indications of treatment modalities,the occurrence of severe adverse events,and the optimal fit for the population.In this review,we provide an update on the treatment modalities available for patients with HCC involving PVTT.Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease:Current Progresses and Challenges

The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an updated literature review detailing epidemiology,risk factors,pathogenic pathways,and treatment strategies linked to NAFLD-related HCC,we conducted a literature search on PubMed from its inception to December 31,2021.About 25%of the global population suffers from NAFLD.The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years.Older age,male sex,metabolic comorbidities,unhealthy lifestyle habits(such as smoking and alcohol consumption),physical inactivity,genetic susceptibility,liver fibrosis,and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC.Therefore,low-calorie diet,moderate-intensity exercise,treatment of metabolic comorbidities,and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC.In addition,all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC.Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC.Hepatic resection,liver transplantation,ablation,transarterial chemoembolization,radiotherapy,targeted drugs,and immune checkpoint inhibitors are used to treat NAFLD-related HCC.Lenvatinib treatment may lead to better overall survival,while immune checkpoint inhibitors may lead to worse overall survival.Given the specific risk factors for NAFLD-related HCC,primary prevention is key.Moreover,the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.

The upward trend in the immunotherapy utilization for hepatobiliary cancers

Hepatobiliary cancers(HBCs)include those of the liver[mainly hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma]and biliary tract(extrahepatic cholangiocarcinoma and gallbladder cancer).Based on the 2020 global cancer statistics,liver cancer ranks seventh in incidence and third in mortality among all malignant tumors,while gallbladder cancer ranks 25th in incidence and 21st in mortality(1).Due to the lack of typical symptoms and signs at the early stages,HBCs are often diagnosed at intermediate or advanced stages,and thus the opportunity of curative surgical interventions is missed(2).Therefore,most patients with HBC can only be treated with noncurative treatments,including immunotherapy.Several immunotherapeutic approaches have been attempted for HBCs,including oncolytic viruses,tumor vaccines,adoptive immunotherapy,and immune checkpoint inhibitors(ICIs;Figure 1).