Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes of liver disease

Chronic infections with the hepatitis B and C viruses have significant worldwide health and economic impacts.Previous treatments for hepatitis C such as interferon and ribavirin therapy were ineffective and poorly tolerated by patients.The introduction of directly acting curative antiviral therapy for hepatitis C and the wider use of nucleos(t)ide analogues for suppression of chronic Hepatitis B infection have resulted in many positive developments.Decreasing the prevalence of hepatitis B and C have concurrently reduced transmission rates and hence,the number of new infections.Antiviral treatments have decreased the rates of liver decompensation and as a result,lowered hospitalisation and mortality rates for both chronic hepatitis B and C infection.The quality of life of chronically infected patients has also been improved significantly by modern treatment.Antiviral therapy has stopped the progression of liver disease to cirrhosis in certain patient cohorts and prevented ongoing hepatocellular damage in patients with existing cirrhosis.Longer term benefits of antiviral therapy include a reduced risk of developing hepatocellular carcinoma and decreased number of patients requiring liver transplantation.This review article assesses the literature and summarises the impact of modern antiviral therapy of chronic hepatitis B and C on clinical outcomes from liver disease.

Double-negative T cells:a promising avenue of adoptive cell therapy in transplant oncology

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer.In addition to the common mechanisms underlying tumor recurrence,another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis.Transplant oncology is an emerging field that addresses oncological challenges in transplantation.In this context,a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients.Double-negative T cells(DNTs)are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor(TCR)type.Among them,TCRαβ^(+)DNTs are considered to induce immune suppression in immune-mediated diseases,while TCRγδ^(+)DNTs are widely recognized as tumor killers.As a composite cell therapy,healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host.In this work,we summarized the biological characteristics and functions of DNTs in oncology,immunology,and transplantation.Based on the multiple roles of DNTs,we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy(ACT).

Enhancement of T cell infiltration via tumor-targeted Th9 cell delivery improves the efficacy of antitumor immunotherapy of solid tumors

Insufficient infiltration of T cells severely compromises the antitumor efficacy of adoptive cell therapy(ACT)against solid tumors.Here,we present a facile immune cell surface engineering strategy aiming to substantially enhance the anti-tumor efficacy of Th9-mediated ACT by rapidly identifying tumor-specific binding ligands and improving the infiltration of infused cells into solid tumors.Non-genetic decoration of Th9 cells with tumor-targeting peptide screened from phage display not only allowed precise targeted ACT against highly heterogeneous solid tumors but also substantially enhanced infiltration of CD8+T cells,which led to improved antitumor outcomes.Mechanistically,infusion of Th9 cells modified with tumor-specific binding ligands facilitated the enhanced distribution of tumor-killing cells and remodeled the immunosuppressive microenvironment of solid tumors via IL-9 mediated immunomodulation.Overall,we presented a simple,cost-effective,and cell-friendly strategy to enhance the efficacy of ACT against solid tumors with the potential to complement the current ACT.