Abstract:

Among the leading causes of cancer related cancer mortality is liver cancer which if often referred
to as hepatocellular carcinoma. Depending on the condition of patient various treatments are
available for liver cancer and among them surgical resection or liver transplant is the principle
treatment for end stage liver cancer. The most commonly used synthetic therapy as a medical
treatment for HCC is sorafenib. Other generally effective treatments includes chemotherapy and
radiotherapy which have less or more side effects. New treatments are needed due to the poor
prognosis of patients with HCC. This article provides an update on the current and future medical
treatment of HCC.
Key words: Transplant, HCC, sorafenib

Introduction:
Currently the sixth most common cancer is hepatocellular carcinoma. It is considered as second
leading cause of death due to cancer in men and sixth for women. The most HCC cases are detected
in advance stages which leads to incurable disease stage (RS, Feb. 2013)
Sorafenib is the only approved medication for advanced HCC. Other may include chemotherapy ,
radiotherapy. But t there is a great need for new techniques treatments and therapies. (Massabki,
2010)

Figure 1avaiable medical and surgical treatments of HCC

Risk factors/causes:

HCC is often associated with liver cirrhosis that results from chronic liver diseases HBV , HCV
infection or auto immune diseases. Excessive alcohol consumption, NASH , non alcoholic fatty
liver disease , exposure and ingestion of aflatoxins , diabetes mellitus etc are other risk factors of
HCC (El-Serag, 2012). The alcohol is metabolized into acetaldehyde which is highly toxic to the
liver cells and can cause the formation of adducts that can inactivate glutathione peroxide system
and can cause mitochondrial damage . (El-Serag, 2013) (McGlynn and London, 2011) NAFLD is
another risk factor for prognosis of HCC (Gomes et al., 2013). About 70% of people with diabetes
and 90% people with obesity are infected with NAFLD. So we can say that NAFLD is a high risk
factor for HCC ((Liao et al., 2012).
Due to the inflammation resulting from fat accumulation in the liver NAFLD can cause NASH ,
cirrhosis and HCC ((Pocha et al., Starley et al., & Michelotti et al., 2015, 2010, 2013).
Tobacco consumption is the potential risk factor for the development of hepatocellular carcinoma
according to the study conducted in EUROPE .

Figure 2risk factors for the development of HCC

Current and former treatments:
1)Synthetic radiotherapy and chemotherapy:
HCC was treated with radio and chemotherapy previously but there are a lot of side effects
associate with these therapies and these have proven to be poor treatments. Among all the tumors
HCC is considered as chemo-resistant. Doxorubicin is considered as one of the most common
among the chemotherapeutic drugs although it does not show response and effectiveness in almost
90% of the cases of HCC.
Treatment with radiotherapy plays a minor role in HCC because like chemotherapy HCC is also
considered to be resistant against radiotherapy. The p53 gene expression and other gene
expressions involved in cell death and division may provide the basis for the development of
resistance for radiotherapy.

2)Sorafenib:
The development of sorafenib in 1990 is the result of ongoing development of
therapies for HCC. After the invention of sorafenib it was rapidly approved by FDA.
An oral multi-kinase inhibitor , a sorafenib inhibits the cell proliferation. Initially
approved by FDA sorafenib was only used for the treatment of metastatic renal
carcinoma and after that it was approved for HCC management.
Still an unmet need for new effective therapies for HCC is required.
Figure 3mechanism of sorafenib action

Current and former medical treatments:

HCC targeted medication is now under focus. Several therapies including epidermal growth factor
receptor , lapatinib , erlotinib , MKF1/2 inhibitor factor are under development which may be more
effective.

1)Oncolytic viral therapy:

Now a days more attention has been put towards oncolytic viral therapy. This therapy is a
promising therapeutic approach for cancer treatment. In this therapy viruses are genetically
engineered to remove their pathogenicity can kill cancer cells by activating immune response
without harming the normal cells.
Mechanism of oncolytic viral therapy is described in fig4.
Figure 4mechanism of oncolytic viral therapy

2)Immunotherapy :
Immunotherapy has revolutionized cancer treatment now a days. Cytotoxic t lymphocyte
associated protein 4 and the programmed cell death protein 1 pathways these two checkpoint
inhibitor are developed for HCC. Regarding immunotherapy in HCC several preclinic and
clinical studies has been published.

Surgical treatments:
Minimally invasive procedures such as TACE, REA, HIFU, MWA, AND IRE ETC can be offered
to those who are not candidate for major surgical therapy. A high number of re-occurrence has
been reported in all these therapies.

1)Trans-arterial chemoembolization (TACE):

For intermediate HCC patients TACE has been indicated as the first treatment. For the Patients
awaiting liver transplantation, TACE has been given as bridging therapy. TACE gives benefit of
2 year survival for end stage HCC. Post embolization syndrome in which abdominal pain , elevated
temperature etc occurs has been associated in TACE adverse events.

2)Radiofrequency Ablation (REA):

First FDA approved REA was obtained in 2001 although it was first developed in 1994. In this
technique rapid electromagnetic pluses that cause thermal injury leading to necrosis of tissues are
applied. REA is considered to be one of the most effective and alternative for surgical resection.
The profile of REA safety is high as its side effects are minimal.

3)Microwave ablation(MWA) :
In this treatment of HCC high electromagnetic waves ranging from 1_300 GHz are given to the
tissues. This treatment has several advantages over REA as in this higher waves are used and the
time duration of treatment is less and the burning risk of skin is low.

4)Irreversible electroporation(IRE):
It is used as electro-chemotherapy in which short electric pluses are used to disrupt the
permeability of cell membrane. This treatment causes holes in cell membrane which leads to cell
death. It has been reported to effect the tumor cells accurately without disturbing or effecting the
normal cells.

Liver transplantation:
Liver transplantation is the surgical therapy for the treatment of end stage HCC. In this procedure
a part of liver is taken from the donor and inserted into the patient. This therapy is based on the
principle that liver regenerate from a part of liver even a smaller part. So by removing the infected
liver of patient and replacing it with part of healthy liver eradicate the disease. Survival rate of
liver transplant is lower. Many complications are there and many critical stages such as donor
matching etc makes it complicated.