Occurrence of hepatocellular carcinoma

I have so far been talking about cancer formation in the adult that would develop as a lifestyle related disease wherever it is in our body in this series. The occurrence of hepatocellular carcinoma does not fall into that category. As a matter of fact, a certain trigger of its occurrence as an initiator of cancer formation is not a lifestyle related disease, but an infection-related disease. However, its promoter is most probably thought to be life-style related disease in terms of chronic inflammation for more than 20 years. This is the reason why I mention in this chapter and is to accord with clients’ claim.

The initiator of its occurrence in Japan is highly suggestive of chronic viral infection such as hepatitis B virus (HBV) or hepatitis C virus (HCV), leading to liver cirrhosis as a consequence of chronic inflammation in the liver for more than 20 years.
In the western countries, hepatocellular carcinoma could occur as a consequence of long term alcohol abuse with chronic inflammation, leading to the same condition as viral infection in the liver. These two factors are considered to be the major causes of liver cirrhosis with chronic inflammation and eventually, more than 90% of the cases with advanced stage of chronic hepatitis or liver cirrhosis will develop hepatocellular carcinoma.

Therefore, people without chronic viral infection or alcohol abuse are certainly not concerned about the risk of developing liver cancer. People who are predisposed to occur hepatocellular carcinoma are quite different groups from the normal population. In accordance with modern medical history, chronic inflammation due to a parasitic worm species called Schistosoma japonica in Asian countries has also been an important cause of liver cirrhosis followed by hepatocellular carcinoma. Nowadays in Japan, this is considered as a disease of the past.

Cell population of the liver function

The liver is composed of hepatocytes and bile duct cells, representing function of the liver. The former is the proper function of the liver called epithelial cells capable of the liver function. HBV or HCV could infect hepatocytes. Hepatocellular carcinoma is derived from hepatocytes.

On the other hand, bile duct cells is the inner cells of the bile duct, through which bile excreted by the hepatocytes flows to the gut. Bile duct carcinoma, or cholangio- celluar carcinoma is derived from the bile duct cells. This cancer is not related with HBV nor HCV and quite rare compared with the former in terms of the prevalence rate in Japan as well as other developed countries.

Hepatitis B and hepatitis C viruses

First of all, I have to discuss about chronic hepatitis caused by the two major viruses. Before the discovery of these viruses, there had been a number of scientific struggles to investigate the infectious routes to humans for a couples of decades since 1950s. These viral infections appeared to be closely related to blood transfusions. HBV (DNA group) was discovered in the contaminated blood samples by Dr. Blumberg in 1970s. His work earned him the Nobel prize. HCV(RNA group) was discovered in the 1990s by a new sophisticated discipline. Tests for detection of these viral markers in the blood have been quite useful in checking for viral contamination of blood samples. Thereafter, incidence of these viral infection via blood transfusions have decreased revolutionalily. However, it should be emphasized that sexual intercourse or vertical transmission from some carrier-mothers to their children can also be a potential route as a parenteral route of infection in a small group of patients.

Host-parasite relationship

Generally speaking, relationships between animal species or plants and any virus have strict selectivity of infections, in terms of molecular interaction between them. HBV or HCV is able to infect only hepatocytes from humans or chimpanzee. As you can see, avian or swine influenza virus can only infect each specific species. However, only mutated viruses could infect human beings. Since birds with mutated avian influenza virus could be flying over the oceans or continents for a short period, we, people over the earth, should absolutely be scared about the great outbreak. HIV mutated from Simian IV (SIV) and SARS transformed from corona virus follow the same pattern.

There is a strict molecular rule between host and parasite relationship in viral infections as mentioned just above. The host has a defense system against viral infection by utilizing the immune system. If the so-called acute infection and immune system response can handle viruses, then they will be eliminated via production of antibodies against them. However, the immune system of our body has a lot of weakness regarding infectious agents, especially HBV or HCV. These agents have a tendency to not be eliminated, but instead to induce a course of chronic inflammation in the liver, transforming normal lobules to pseudo-lobules in the hepatic functional units. This condition is called liver cirrhosis, or fibrosis of the liver caused by scar formation, with inflammation and on-going viral persistence.

Free radicals released by inflammatory cells and DNA damage

Free radicals, generated by inflammatory cells such as macrophages and neutrophiles, could cause continuing damage to hepatocytic DNA, and then the damaged DNA replicates followed by summing up randomly to damage exon sites in terms of mutated genes. This cause and effect is a common pattern in cancer development. Hepatocellular carcinoma tends to be a lifestyle-related disease in adults, which I have mentioned in previous articles. Therefore, chronic inflammation is one of the key attributes in the development of cancer.

Clinically, there is significant difference in the possible outcome of cirrhosis with or without chronic inflammation leading to hepatocellular carcinoma when cirrhosis is caused by HBV versus HCV. Specifically, the latter with a likely tendency to continue chronic inflammation to cause hepatocellular carcinoma after 10 years later since beginning of liver cirrhosis. On the other hand, in the cases with cirrhosis caused by hepatitis B, development of hepatocellular carcinoma tends to be slow down after 5 years. Inflammation levels in the liver can be measured by liver biopsy evaluated and diagnosed by board-certified pathologists in Japan like me.

After developing cirrhosis, strong inflammatory reactions are likely to lead to hepatocellular carcinoma. In light of this, one should consider traditional Chinese medicine that suppresses inflammation, or functional foods like BioBran, which are anti-inflammatory, after developing cirrhosis.

On the other hand, various medicines have been developed to cure hepatitis by killing the virus, but they are not effective enough on some specific viruses. In order to prevent hepatocellular carcinoma, it is critical and important not only to eliminate the virus, but also to suppress inflammatory processes.

Even if a patient does occur hepatocellular carcinoma, various supportive approaches, including ideal eating habits, functional foods, and improving lifestyle will help delay the progression of cirrhotic process, and support liver function followed by delay carcinogenesis of the cirrhotic liver.

Application of BioBran, a modified rice bran, for preventing development of hepatocellular carcinoma as an anti-inflammatory supplement

Elimination of HBV or HCV in its chronic phase of infection is still quite hard, even with sophisticated drug treatment. Chronic hepatitis caused by chronic viral infection is also considered to be a significant cause of hepatocellular carcinoma. This is the same kind of consequence that occurs with chronic inflammation in other organs in the life style related disease. This consequence may most probably lead to cancer development, as mentioned in previous chapters.

BioBran is a product of rice bran and basically is a compound of polysaccharides, namely arabinoxylan. BioBran is an enriched plant-fiber, specifically arabinoxylan, which is a kind of polysaccharide compound. This supplement has been investigated in in vitro and in vivo studies, as well as in several clinical studies. A number of papers have been published in the peer-reviewed journals regarding its function. This supplement has a potent immunomodulating action by supporting immune homeostasis and the body’s natural healing powers. Allergies are considered as over-active immune responses consisting of chronic inflammatory reactions due to a variety of causes which can be uniquely regulated or modulated by this supplement. Long term modulation of these over-reactions is necessary, especially for cancer prevention, because decreasing chronic inflammation prevents cancer promotion. Moreover, recently, Dr.Ghoneum and Vietnamese clinicians published clinical studies concerning efficacy of suppression of cancer cell growth of hepatocellular carcinoma by BioBran in the journal named Anticancer Research.

Conclusions

When we look back to the history of medical research, it is very important to ask the question “is hepatocellular carcinoma in human caused by HBV or HCV viral genome?” Ultimately, there is no direct evidence that viral genome is built into host DNA or RNA, or causes infected hepatocytes to become cancerous growth. I would like to answer “No” to the above question as described in my hypothesis, based on current knowledge. Therefore, decrease of chronic inflammation by BioBran or other immunomodulators whatever it is prevents promotion of cancer formation in terms of chemoprevention.