Hepatocellular carcinoma treatment: hurdles, advances and prospects

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality and is particularly refractory to the available chemotherapeutic drugs. Among various etiologies of HCC, viral etiology is the most common, and, along with alcoholic liver disease and nonalcoholic steatohepatitis, accounts for almost 90% of all HCC cases. HCC is a heterogeneous tumor associated with multiple signaling pathway alterations and its complex patho-physiology has made the treatment decision challenging. The potential curative treatment options are effective only in small group of patients, while palliative treatments are associated with improved survival and quality of life for intermediate/advanced stage HCC patients. This review article focuses on the currently available treatment strategies and hurdles encountered for HCC therapy. The curative treatment options discussed are surgical resection, liver transplantation, and local ablative therapies which are effective for early stage HCC patients. The palliative treatment options discussed are embolizing therapies, systemic therapies, and molecular targeted therapies. Besides, the review also focuses on hurdles to be conquered for successful treatment of HCC and specifies the future prospects for HCC treatment. It also discusses the multi-modal approach for HCC management which maximizes the chances of better clinical outcome after treatment and identifies that selection of a particular treatment regimen based on patients' disease stage, patients' ages, and other underlying factors will certainly lead to a better prognosis.

Keywords: Hepatitis; anti-virals; cell-therapies; curative treatment; hepatocellular cracinoma; palliative treatment; regorafenib; sorafenib; transarterial chemoembolization; xenotransplantaion.

Figure 1.. Classification of available hepatocellular carcinoma therapies based on the stages of patients.

Curative therapies are suitable for early stage patients and includes surgical resection, liver transplantation, and local ablative therapies. Physical ablation can be by done any energy source, which works by heating (radiofrequency, microwave, and laser) or cooling (cryo/freeze–thaw) of tumor affected area. Palliative therapies includes embolizing, systemic and molecular targeted therapies. CPT: Cisplatin; DXR: Doxorubicin; HCC: Hepatocellular carcinoma; MMC: Mitomycin C; PEI: Percutaneous ethanol injection; PIAF: Cisplatin, interferon, adriamycin, and fluorouracil.

Figure 2.. Hurdles in hepatocellular carcinoma treatment classified as level 1, level 2 and level 3.

Level 1 includes hurdles encountered at screening and diagnosis which involves asymptomatic disease, poor awareness of patient, lack of resources, as in case of low middle income countries, and patient's inability to pay for the tests. Educational hurdles include both poor patient's education and insufficient knowledge of healthcare provider. Level 2 includes treatment decision and acceptance of the treatment strategies and involves picking right treatment strategy based on the stage and liver function status. Level 3 includes hurdles in hepatocellular carcinoma (HCC) treatment at molecular level which holds potential to investigate various molecular changes observed in HCC patients. All these hurdles show the way to several prospects for HCC treatment which include prophylactic measures, xenotransplantion with pig liver, cell therapies and targeting awry molecules/pathways. The dotted lines in the flowchart depicts correlated aspects of hurdles and prospects. BAL: Bio-artificial liver; HCC: Hepatocellular carcinoma; PHT: Primary hepatocyte transplantation; RAAS: Renin–angiotensin–aldosterone system.