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We Cure Viral Diseases with Non-Pathogenic Viruses!

Hepatocellular Carcinoma Program

Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer and results in more than 600,000 global deaths per year with an increasing incidence mainly because of the spread of hepatitis C virus (HCV) infection. HCC is two diseases in one: underlying liver dysfunction and the cancer itself, both of which require care intensive management. Scoring systems incorporating both liver dysfunction as well as cancer-related factors are valuable when formulating a treatment strategy.

In our view, HBV/ HCV positive HCC patients are an ideal niche population for testing the safety and efficacy of SIT for the following reasons. The most influential factor for the development of HCC is ongoing inflammation in the liver. Chronic HBV and HCV carriers have up to 15- to 17-fold increased risk of HCC. The longer the inflammation persists, the higher the risk of associated carcinogenesis. Cancer risk increases sharply at the cirrhosis stage; in fact, cancer develops in 80% of cirrhotic liver (see Figure below).

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The rate of HCC in virus hepatitis patients. In this study patients
born in the USA were investigated at the MD Andersen Medical
Center (Houston, Texas), in whom HCV or HBV infection was
confirmed. The rate of HCC increased only in the HCV positive
population (El-Serag HB, Rudolph KL. Hepatocellular carcinoma:
epidemiology and molecular carcinogenesis. Gastroenterology
2007, 132(7):2557-76).

Partial hepatectomy (PHx) is considered the gold standard of treatment because it aims to “cure” patients with resectable HCC. Unfortunately, only a minority of patients is eligible for potentially curative treatments. The prognosis for advanced HCC that has progressed after loco-regional therapy is poor because this tumor is chemo-resistant. Following curative treatment for HCC, 50%-90% of postoperative death is due to recurrent disease. Intra-hepatic recurrence is frequently the only site of reappearance.

Currently, there is no consensus on a standard neoadjuvant, adjuvant or chemoprevention therapy for advanced HCC. Thus, any neoadjuvant or adjuvant therapy, which can decrease or delay the incidence of intra-hepatic recurrence, or any cancer chemoprevention which can prevent a new HCC from developing in the remnant liver, will improve the results of liver resection. Interferon-alpha has recently been recognized to harbor adjuvant therapeutic potential, especially among sustained virologic or biochemical responders. Unfortunately, IFN-based adjuvant therapy in HCC is associated with significant side effects, which necessitates suboptimal dosing.