I would like this thread to be used for the benefit of all Macedonians who may not know alot about the human body and the types of diseases and illnesses that can occur.
LIVER CANCER ESSAY
Liver cancer is the third in the world of cancer related deaths (WHO, 2009); this topic will look at the epidemiology and pathogenesis of the most common liver cancer, hepatocellular carcinoma. The biological, social, environmental and behavioural factors that accompany epidemiology and pathogenesis of liver cancer will follow. The methods of diagnosing liver cancer will also be discussed.
Important definitions to remember; Hepatocellular carcinoma is a malignancy of the liver (Feldman et al, 2006). Alanine aminotransferase (ALT) is an enzyme that converts L-alanine and D-alanine and visa versa (Feldman et al, 2006). Aspartate aminotransferase (AST) is an enzyme, it catalyses aspartate which reacts with 2-oxoglutarate the end result is oxaloacetate and glutamate (Feldman et al, 2006). The pigment of bile is referred to as bilirubin; it is formed from the breakdown of haemoglobin (Feldman et al, 2006).
Epidemiology of Hepatocellular Carcinoma of the Liver
The most common liver cancer is hepatocellular carcinoma (HCC). The incidence for this type of carcinoma of the liver is increasing to a point where it is now fifth on the list of common malignancy in the world; it is also the third leading cause of death related cancer (WHO, 2009). Data that has been collected suggests that new cases amount to 500,000 – 1,000,000 per year, out of these figures 600,000 deaths occur worldwide annually (Parkin et al, 1999). On a global level there are however differences in the level of HCC between countries and is only now being looked at as a factor that may link certain populations who have an increased risk (Parkin et al, 1999).
The world Health Organisation (WHO) has pointed out that a lot of the cases of HCC are in fact coming out of Asia. Montalto (et al, 2002) confirmed that in East Asia the incidence here are very high, on Mongolia 99 per 100,000 people, Korea 49 per 100,000, Japan 29 per 100,00, and in China 35 per 100,000 (Montalto et al, 2002). The western region of Africa is also a place of concern, places such as Gambia, Guinea and Mali. Italy, Spain and Latin America are not exempt and have high risks, 11 cases per 100,000 to 20 cases per 100,000 found in these countries (Montalto et al, 2002). The countries that are intermediate happen to be in Europe with 5 cases per 100,000 to 10 cases per 100,000 occurring in France, the United Kingdome, and Germany (Montalto et al, 2002). The lowest incidences occur in the United States, Canada and in Scandinavia with less than 5 cases per 10,000 people (Montalto et al, 2002) (Parkin et al, 1999).
Montalto and his colleagues (et al, 2002) have found that in developed countries that are at low risk such as the United States the incidence of HCC are rising by 80% per year in the past 20 years (Montalto et al, 2002) (Parkin et al, 1999). The study reveals that African-American men are more prone to HCC than US Caucasian men; this is seen in the high cases of hepatitis C and the rise in immigration from countries that are high risk have also played a part (Montalto et al, 2002). Other countries, Montalto (et al, 2002) and Parkin (et al, 1999) have noted, Italy, the United Kingdome, Canada, Japan and, Australia have all recorded increased cases of HCC, these increases were from immigrants from Sub-Saharan African countries and parts of Asia where there is a high prevalence of HCC.
A report that was conducted by Jong-Wook (et al, 2003) in conjunction with the World Health Organisation (WHO) in 2003, that a total of 714,600 new cases of HCC have been recorded globally, this accounts for 71% among men. With the findings of Seeff (et al, 2006) geographically the results show “45,000 liver cancer deaths happen in Africa, 37,000 in the Americas, 15,000 in the eastern Mediterranean, 67,000 in Europe, 61,000 in south-east Asia , and 394,000 in the western Pacific region which includes China and Japan” (Seeff et al, 2006). In 2006, 501,000 men and 282,000 women died of cirrhosis with a combined total of 783,000 persons (Seeff et al, 2006). From this study Seeff (et al, 2006) found that HCC increased with age and that when a person reached the age of 65 years it had a high prevalence, he noted that before the age of 50 it was rare for someone from North America and Western Europe to get HCC. Nonetheless there has been a slight shift to suggest that HCC is becoming higher in the younger population (Seeff et al, 2006)
Pathogenesis of Hepatocellular Carcinoma
The focus will be put on how hepatocellular carcinoma is linked to TP53 mutation, aflatoxin B1 (AFB1) and how infection by hepatitis B and C can have a direct affect in the progression to liver cancer.
Aflatoxin B1
Bressac (et al, 1991) looked at the mutational spectrum of hepatocellular carcinoma and has found that cancer can form with carcinogen exposure. In the study it was observed that geographical areas that have a diet exposed to AFB1, which contains foods like corn, rice and peanuts and also areas such as China and Africa which have high rates of chronic viral hepatitis (Bressac et al, 1991). This will give rise to a point mutation which results in a transversion of G: C to T: A due to the third position of codon 249ser (Bressac et al, 1991). Kirk and colleagues (et al, 2005) studied patients from Gambia with HCC, they found that that in serum DNA codon 249 mutation could be noticed, this meant that it was possible for TP53 to be a biomarker due to the exposure to AFB1 and early hepatocellular carcinoma (Kirk et al, 2005)
With an active AFB1 it mutates and to binds to DNA by 8, 9-epoxide to form promutagenic N7dG (Bressac et al, 1991) (Kirk et al, 2005) oxidative and nitrosative stress from AFB1 can cause TP53 249ser mutation via lipid deoxidisation (Bressac et al, 1991). Without the exposure of AFB1 it is not common for there to be a TP53 249ser mutation, this applies to HBV or HCV infection (Bressac et al, 1991). At this stage it is not known if AFB1 by itself can cause HCC without HBV infection in a population, it is however known that when HBV and AFB1 are together there is a high number of TP53 249ser mutations in HCC (Bressac et al, 1991) (Ming et al, 2002)
Hepatitis B Virus (HBV)
The two main hepatitis viruses that contribute to liver carcinogenesis are HBV and HCV; they produce liver injury and are promoters of hepatocarcinogenesis. There are still studies being conducted to verify if hepatitis infections cause the tumours or if inflammation that leads to liver cancer and cirrhosis has an affect on tumour promotion in hepatocarcinogenesis (Tang et al, 2006).
The viral proteins of HBV and HCV in order to survive have to interact with the bodies proteins which they change, this alters the cellular gene expression, and it is thought that this process can lead to virus – associated carcinogenesis (Tang et al, 2006). Hepatitis B is a partially double stranded DNA molecule and is a hepadna virus (Tang et al, 2006) for the viral protein to have any affect it needs the gene X of HBV which is named HBx, this is needed in transcription of the viral gene (Tang et al, 2006).
Tang (et al, 2006) has focused on the HBx protein which has a strong role in HCC. The HBx gene is the most currently open HBV gene (Tang et al, 2006). Binding of p53 is reduced by HBx and inhibits nucleotide excision repair and in transcription, it interacts with other DNA enzymes (Tang et al, 2006) (Mathonnet et al, 2004). Mathonnet (et al, 2004) and Tang (et al, 2006) make a note of the fact that when HBx directly interferes with the normal cellular DNA repair system it leads to HBV contribution to liver carcinogenesis. If the function of p53 – mediated apoptosis is lost two factors that could be favourable in contributing to hepatocellular carcinogenesis are neoplastic hepatocytes or preneoplastic (Mathonnet et al, 2004)
Hepatitis C Virus (HCV)
To get an idea of how HCV affects hepatocellular carcinogenesis Honda (et al, 2001) uses microarray technology, it analyses HCV in relation to cirrhosis. It has shown that this leads to up regulation of pro – inflammatory, pro – apoptotic and pro – proliferative genes, all of these factors result in hepatitis C associated with cirrhosis to lead to hepatocellular carcinogenesis (Honda et al, 2001). With HCV the TP53 tumours have a greater potential to become malignant according to Honda (et al, 2004).
Biological Factors
Epidemiologically it has been discussed that hepatitis B and C can have a direct affect on p53 to alter its genetic makeup and use the body’s proteins to make more HBx proteins in the liver (Tang et al, 2006) (Mathonnet et al, 2004). With the p53 gene altered in a state that can defect and mutate more readily it adds to the pathogenesis and increases the risk of hepatocellular carcinoma of the liver.
Social Factors
When looking at social factors that might influence liver cancer it is imperative to include the economic and employment status of an individual. In a Swedish study conducted by Ji (et al, 2005) different social groups were looked at to see if a persons profession could in fact be a factor in increasing the likelihood of liver cancer. The study used data from the 1960 and 1970 census and did a follow up study to compare new data that has been collected. It was found that male farmers were at a low risk to all types of liver cancers including HCC and professionals such as executives and those that had private businesses (Ji et al, 2005).
Behavioural Factors
Montalto (et al, 2002), Parkin (et al, 1999) and the WHO all give data to support alcohol as a factor in fatty liver disease which leads to liver cancer. Diet is something else that has been mentioned by Bressec (et al, 1991), contamination of foods like rice, corn and peanuts by AFB1.
Environmental Factors
With reference to geographical regions Africa and East Asia have increased risk of developing hepatocellular carcinoma and any other type of liver cancer due to HBV or HCV infection (Montalto et al, 2002) (Parkin et al, 1999) (Jong-Wook et al, and WHO 2005) and (Seeff et al, 2006). It could also have something to do with the chemicals from the environment that can contaminate food (Bressac et al, 1991).
Methods of Diagnosis
With diagnosis there isn’t a specific test that is performed but rather a variety of tests that look at detecting hepatitis and other abnormalities such as the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin.
Alanine aminotransferase (ALT) is used as a method to identify patients with liver disease as it detects liver cell injury and hepatocellular damage (Feldman et al, 2006). Recently, ALT is the most used test to identify serum ALT level in patients with liver disease (Feldman et al, 2006).
Aspartate aminotransferase (AST) concentration can be elevated in heart and liver diseases that are connected to the destruction of those tissues via the blood (Feldman et al, 2006). The normal levels of AST are from 8 to 20 U/l, these levels can change depending on the reply it gets from to the magnitude of cellular necrosis (Feldman et al, 2006).
Bilirubin is also important in detecting liver cancer, after its production it is taken to the plasma and then the liver where it will be excreted in the bile. Increased amounts of bile in the blood of>30 mg/l will lead to jaundice (Feldman et al, 2006).
When HCC occurs ALT enters the bloodstream as it is secreted from the liver cells, this in tern increases the serum level which would give a high result. The normal levels for Alanine aminotransferase are from 10 to 32 U/l and in women range from 9 to 24 U/l (Feldman et al, 2006). In an infant it is twice the amount of an adult (Feldman et al, 2006). In acute viral hepatitis an increase in serum transaminase activity is due to an increase in one particular aminotransferase, ALT which in the period of acute hepatitis B it can increase from a mild increase of 10 times the normal amount to a startling increase of 100 times the normal amount (Feldman et al, 2006). In most patients’ symptoms such as tiredness, abdominal discomfort which leads to anorexia can in turn can make a patient feel nauseas and make them vomit, all these symptoms can lead to the patient developing jaundice, with regards to fever it is generally mild and may not appear at all (Feldman et al, 2006).
A sudden drop in ALT and AST in patients with fulminate hepatic failure it can be understood as the clearing of hepatic infection, this ultimately comes down to a deadly outcome as hepatocytes are being lost (Feldman et al, 2006).
It is important to understand that liver cancer is on the rise and the number of people diagnosed will increase. By studying the epidemiology it is becoming clear that there are trouble spots around the world where this disease is prevailing and in most cases the number one killer, this has lead to an effort to study the pathogenesis of liver cancer and in particular hepatocellular carcinoma and its relationship with hepatitis B and C to a greater extent. New methods specific in detecting liver cancer should be designed to ensure fast and early detection as it is the key in preventing and stopping the spread to other organs. It is certain however those behavioral factors such as excessive alcohol consumption have a negative effect on the liver. Social status has shown that people that have stressful jobs are more inclined to aid in HCC. Contamination of food due to the environment has also been considered.
References
Bressac B, Kew M, Wands J, Ozturk M, 1991.’Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa’. Nature. Volume 350, pp. 429–431. Viewed 18 August 2009, retrieved from EBSCOhost.
Feldman M, Friedman L S, Brandt L J, 2006. Saunders, ‘Nonalcoholic fatty liver disease. Gastrointestinal and Liver Disease’. Eighth edition. Canada. pp. 1793–1805.
Honda M, Kaneko S, Kawai H, Shirota Y, Kobayashi K, 2001. ‘Differential gene expression between chronic hepatitis B and C hepatic lesion’. Gastroenterology. Volume 120, pp. 955–966. Viewed 18 August 2009, retrieved from EBSCOhost.
Ji J & Hemminki K, 2005. ‘Variation in the risk for liver and gallbladder cancers in socioeconomic and occupational groups in Sweden with etiological implications’. International Archives of Occupational and Environmental Health. Volume 78, pp. 641-9. Viewed 18 August 2009, retrieved from EBSCOhost.
Jong-wook L. and WHO, 2003. ‘Shaping the future’. Global health improvement. Volume 362, pp. 2083-2088. Viewed 18 August 2009, retrieved from EBSCOhost.
Kirk GD, Lesi OA, Mendy M, Szymanska K, Whittle H, Goedert JJ et al, 2005. ‘249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma’. Oncogene. Volume 24, pp. 5858–5867. Volume 120, pp. 955–966. Viewed 18 August 2009, retrieved from EBSCOhost.
Mathonnet G, Lachance S, Alaoui-Jamali M, Drobetsky EA, 2004. ‘Expression of hepatitis B virus X oncoprotein inhibits transcription-coupled nucleotide excision repair in human cells’. Mutat Res. Volume 554, pp. 305–318. Viewed 18 August 2009, retrieved from EBSCOhost.
Ming L, Thorgeirsson SS, Gail MH, Lu P, Harris CC, Wang N et al, 2002. ‘Dominant role of hepatitis B virus qand cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China’. Hepatology. Volume 36, pp. 1214–1220. Viewed 18 August 2009, retrieved from EBSCOhost.
Montalto G, Cervello M, Giannitrapani L, Dantona F, Terranova A, Castagnetta LA, 2002. ‘Epidemiology, risk factors, and natural history of hepatocellular carcinoma’. New York Academy of Science. Volume 963, pp.13-2. Viewed 18 August 2009, retrieved from EBSCOhost.
Parkin DM, Pisani P, Ferlay J, 1999. ‘Estimates of the worldwide incidence of 25 major cancers in 1990. International journal of Cancer. Volume 80, pp. 827-841. Viewed 18 August 2009, retrieved from EBSCOhost.
Seeff LB, Hoofnagle JH, 2006. ‘Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity’. Oncogene. Volume 25, pp. 3771-3777. Viewed 18 August 2009, retrieved from EBSCOhost.
Tang H, Oishi N, Kaneko S, Murakami S, 2006. ‘Molecular functions and biological roles of hepatitis B virus x protein’. Cancer Science. Volume 97, pp. 977–983. Viewed 18 August 2009, retrieved from EBSCOhost.
World Health Organization, 2009. Mortality database. <http://www.who.int/whosis/en>. Viewed 18 August 2009.
LIVER CANCER ESSAY
Liver cancer is the third in the world of cancer related deaths (WHO, 2009); this topic will look at the epidemiology and pathogenesis of the most common liver cancer, hepatocellular carcinoma. The biological, social, environmental and behavioural factors that accompany epidemiology and pathogenesis of liver cancer will follow. The methods of diagnosing liver cancer will also be discussed.
Important definitions to remember; Hepatocellular carcinoma is a malignancy of the liver (Feldman et al, 2006). Alanine aminotransferase (ALT) is an enzyme that converts L-alanine and D-alanine and visa versa (Feldman et al, 2006). Aspartate aminotransferase (AST) is an enzyme, it catalyses aspartate which reacts with 2-oxoglutarate the end result is oxaloacetate and glutamate (Feldman et al, 2006). The pigment of bile is referred to as bilirubin; it is formed from the breakdown of haemoglobin (Feldman et al, 2006).
Epidemiology of Hepatocellular Carcinoma of the Liver
The most common liver cancer is hepatocellular carcinoma (HCC). The incidence for this type of carcinoma of the liver is increasing to a point where it is now fifth on the list of common malignancy in the world; it is also the third leading cause of death related cancer (WHO, 2009). Data that has been collected suggests that new cases amount to 500,000 – 1,000,000 per year, out of these figures 600,000 deaths occur worldwide annually (Parkin et al, 1999). On a global level there are however differences in the level of HCC between countries and is only now being looked at as a factor that may link certain populations who have an increased risk (Parkin et al, 1999).
The world Health Organisation (WHO) has pointed out that a lot of the cases of HCC are in fact coming out of Asia. Montalto (et al, 2002) confirmed that in East Asia the incidence here are very high, on Mongolia 99 per 100,000 people, Korea 49 per 100,000, Japan 29 per 100,00, and in China 35 per 100,000 (Montalto et al, 2002). The western region of Africa is also a place of concern, places such as Gambia, Guinea and Mali. Italy, Spain and Latin America are not exempt and have high risks, 11 cases per 100,000 to 20 cases per 100,000 found in these countries (Montalto et al, 2002). The countries that are intermediate happen to be in Europe with 5 cases per 100,000 to 10 cases per 100,000 occurring in France, the United Kingdome, and Germany (Montalto et al, 2002). The lowest incidences occur in the United States, Canada and in Scandinavia with less than 5 cases per 10,000 people (Montalto et al, 2002) (Parkin et al, 1999).
Montalto and his colleagues (et al, 2002) have found that in developed countries that are at low risk such as the United States the incidence of HCC are rising by 80% per year in the past 20 years (Montalto et al, 2002) (Parkin et al, 1999). The study reveals that African-American men are more prone to HCC than US Caucasian men; this is seen in the high cases of hepatitis C and the rise in immigration from countries that are high risk have also played a part (Montalto et al, 2002). Other countries, Montalto (et al, 2002) and Parkin (et al, 1999) have noted, Italy, the United Kingdome, Canada, Japan and, Australia have all recorded increased cases of HCC, these increases were from immigrants from Sub-Saharan African countries and parts of Asia where there is a high prevalence of HCC.
A report that was conducted by Jong-Wook (et al, 2003) in conjunction with the World Health Organisation (WHO) in 2003, that a total of 714,600 new cases of HCC have been recorded globally, this accounts for 71% among men. With the findings of Seeff (et al, 2006) geographically the results show “45,000 liver cancer deaths happen in Africa, 37,000 in the Americas, 15,000 in the eastern Mediterranean, 67,000 in Europe, 61,000 in south-east Asia , and 394,000 in the western Pacific region which includes China and Japan” (Seeff et al, 2006). In 2006, 501,000 men and 282,000 women died of cirrhosis with a combined total of 783,000 persons (Seeff et al, 2006). From this study Seeff (et al, 2006) found that HCC increased with age and that when a person reached the age of 65 years it had a high prevalence, he noted that before the age of 50 it was rare for someone from North America and Western Europe to get HCC. Nonetheless there has been a slight shift to suggest that HCC is becoming higher in the younger population (Seeff et al, 2006)
Pathogenesis of Hepatocellular Carcinoma
The focus will be put on how hepatocellular carcinoma is linked to TP53 mutation, aflatoxin B1 (AFB1) and how infection by hepatitis B and C can have a direct affect in the progression to liver cancer.
Aflatoxin B1
Bressac (et al, 1991) looked at the mutational spectrum of hepatocellular carcinoma and has found that cancer can form with carcinogen exposure. In the study it was observed that geographical areas that have a diet exposed to AFB1, which contains foods like corn, rice and peanuts and also areas such as China and Africa which have high rates of chronic viral hepatitis (Bressac et al, 1991). This will give rise to a point mutation which results in a transversion of G: C to T: A due to the third position of codon 249ser (Bressac et al, 1991). Kirk and colleagues (et al, 2005) studied patients from Gambia with HCC, they found that that in serum DNA codon 249 mutation could be noticed, this meant that it was possible for TP53 to be a biomarker due to the exposure to AFB1 and early hepatocellular carcinoma (Kirk et al, 2005)
With an active AFB1 it mutates and to binds to DNA by 8, 9-epoxide to form promutagenic N7dG (Bressac et al, 1991) (Kirk et al, 2005) oxidative and nitrosative stress from AFB1 can cause TP53 249ser mutation via lipid deoxidisation (Bressac et al, 1991). Without the exposure of AFB1 it is not common for there to be a TP53 249ser mutation, this applies to HBV or HCV infection (Bressac et al, 1991). At this stage it is not known if AFB1 by itself can cause HCC without HBV infection in a population, it is however known that when HBV and AFB1 are together there is a high number of TP53 249ser mutations in HCC (Bressac et al, 1991) (Ming et al, 2002)
Hepatitis B Virus (HBV)
The two main hepatitis viruses that contribute to liver carcinogenesis are HBV and HCV; they produce liver injury and are promoters of hepatocarcinogenesis. There are still studies being conducted to verify if hepatitis infections cause the tumours or if inflammation that leads to liver cancer and cirrhosis has an affect on tumour promotion in hepatocarcinogenesis (Tang et al, 2006).
The viral proteins of HBV and HCV in order to survive have to interact with the bodies proteins which they change, this alters the cellular gene expression, and it is thought that this process can lead to virus – associated carcinogenesis (Tang et al, 2006). Hepatitis B is a partially double stranded DNA molecule and is a hepadna virus (Tang et al, 2006) for the viral protein to have any affect it needs the gene X of HBV which is named HBx, this is needed in transcription of the viral gene (Tang et al, 2006).
Tang (et al, 2006) has focused on the HBx protein which has a strong role in HCC. The HBx gene is the most currently open HBV gene (Tang et al, 2006). Binding of p53 is reduced by HBx and inhibits nucleotide excision repair and in transcription, it interacts with other DNA enzymes (Tang et al, 2006) (Mathonnet et al, 2004). Mathonnet (et al, 2004) and Tang (et al, 2006) make a note of the fact that when HBx directly interferes with the normal cellular DNA repair system it leads to HBV contribution to liver carcinogenesis. If the function of p53 – mediated apoptosis is lost two factors that could be favourable in contributing to hepatocellular carcinogenesis are neoplastic hepatocytes or preneoplastic (Mathonnet et al, 2004)
Hepatitis C Virus (HCV)
To get an idea of how HCV affects hepatocellular carcinogenesis Honda (et al, 2001) uses microarray technology, it analyses HCV in relation to cirrhosis. It has shown that this leads to up regulation of pro – inflammatory, pro – apoptotic and pro – proliferative genes, all of these factors result in hepatitis C associated with cirrhosis to lead to hepatocellular carcinogenesis (Honda et al, 2001). With HCV the TP53 tumours have a greater potential to become malignant according to Honda (et al, 2004).
Biological Factors
Epidemiologically it has been discussed that hepatitis B and C can have a direct affect on p53 to alter its genetic makeup and use the body’s proteins to make more HBx proteins in the liver (Tang et al, 2006) (Mathonnet et al, 2004). With the p53 gene altered in a state that can defect and mutate more readily it adds to the pathogenesis and increases the risk of hepatocellular carcinoma of the liver.
Social Factors
When looking at social factors that might influence liver cancer it is imperative to include the economic and employment status of an individual. In a Swedish study conducted by Ji (et al, 2005) different social groups were looked at to see if a persons profession could in fact be a factor in increasing the likelihood of liver cancer. The study used data from the 1960 and 1970 census and did a follow up study to compare new data that has been collected. It was found that male farmers were at a low risk to all types of liver cancers including HCC and professionals such as executives and those that had private businesses (Ji et al, 2005).
Behavioural Factors
Montalto (et al, 2002), Parkin (et al, 1999) and the WHO all give data to support alcohol as a factor in fatty liver disease which leads to liver cancer. Diet is something else that has been mentioned by Bressec (et al, 1991), contamination of foods like rice, corn and peanuts by AFB1.
Environmental Factors
With reference to geographical regions Africa and East Asia have increased risk of developing hepatocellular carcinoma and any other type of liver cancer due to HBV or HCV infection (Montalto et al, 2002) (Parkin et al, 1999) (Jong-Wook et al, and WHO 2005) and (Seeff et al, 2006). It could also have something to do with the chemicals from the environment that can contaminate food (Bressac et al, 1991).
Methods of Diagnosis
With diagnosis there isn’t a specific test that is performed but rather a variety of tests that look at detecting hepatitis and other abnormalities such as the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin.
Alanine aminotransferase (ALT) is used as a method to identify patients with liver disease as it detects liver cell injury and hepatocellular damage (Feldman et al, 2006). Recently, ALT is the most used test to identify serum ALT level in patients with liver disease (Feldman et al, 2006).
Aspartate aminotransferase (AST) concentration can be elevated in heart and liver diseases that are connected to the destruction of those tissues via the blood (Feldman et al, 2006). The normal levels of AST are from 8 to 20 U/l, these levels can change depending on the reply it gets from to the magnitude of cellular necrosis (Feldman et al, 2006).
Bilirubin is also important in detecting liver cancer, after its production it is taken to the plasma and then the liver where it will be excreted in the bile. Increased amounts of bile in the blood of>30 mg/l will lead to jaundice (Feldman et al, 2006).
When HCC occurs ALT enters the bloodstream as it is secreted from the liver cells, this in tern increases the serum level which would give a high result. The normal levels for Alanine aminotransferase are from 10 to 32 U/l and in women range from 9 to 24 U/l (Feldman et al, 2006). In an infant it is twice the amount of an adult (Feldman et al, 2006). In acute viral hepatitis an increase in serum transaminase activity is due to an increase in one particular aminotransferase, ALT which in the period of acute hepatitis B it can increase from a mild increase of 10 times the normal amount to a startling increase of 100 times the normal amount (Feldman et al, 2006). In most patients’ symptoms such as tiredness, abdominal discomfort which leads to anorexia can in turn can make a patient feel nauseas and make them vomit, all these symptoms can lead to the patient developing jaundice, with regards to fever it is generally mild and may not appear at all (Feldman et al, 2006).
A sudden drop in ALT and AST in patients with fulminate hepatic failure it can be understood as the clearing of hepatic infection, this ultimately comes down to a deadly outcome as hepatocytes are being lost (Feldman et al, 2006).
It is important to understand that liver cancer is on the rise and the number of people diagnosed will increase. By studying the epidemiology it is becoming clear that there are trouble spots around the world where this disease is prevailing and in most cases the number one killer, this has lead to an effort to study the pathogenesis of liver cancer and in particular hepatocellular carcinoma and its relationship with hepatitis B and C to a greater extent. New methods specific in detecting liver cancer should be designed to ensure fast and early detection as it is the key in preventing and stopping the spread to other organs. It is certain however those behavioral factors such as excessive alcohol consumption have a negative effect on the liver. Social status has shown that people that have stressful jobs are more inclined to aid in HCC. Contamination of food due to the environment has also been considered.
References
Bressac B, Kew M, Wands J, Ozturk M, 1991.’Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa’. Nature. Volume 350, pp. 429–431. Viewed 18 August 2009, retrieved from EBSCOhost.
Feldman M, Friedman L S, Brandt L J, 2006. Saunders, ‘Nonalcoholic fatty liver disease. Gastrointestinal and Liver Disease’. Eighth edition. Canada. pp. 1793–1805.
Honda M, Kaneko S, Kawai H, Shirota Y, Kobayashi K, 2001. ‘Differential gene expression between chronic hepatitis B and C hepatic lesion’. Gastroenterology. Volume 120, pp. 955–966. Viewed 18 August 2009, retrieved from EBSCOhost.
Ji J & Hemminki K, 2005. ‘Variation in the risk for liver and gallbladder cancers in socioeconomic and occupational groups in Sweden with etiological implications’. International Archives of Occupational and Environmental Health. Volume 78, pp. 641-9. Viewed 18 August 2009, retrieved from EBSCOhost.
Jong-wook L. and WHO, 2003. ‘Shaping the future’. Global health improvement. Volume 362, pp. 2083-2088. Viewed 18 August 2009, retrieved from EBSCOhost.
Kirk GD, Lesi OA, Mendy M, Szymanska K, Whittle H, Goedert JJ et al, 2005. ‘249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma’. Oncogene. Volume 24, pp. 5858–5867. Volume 120, pp. 955–966. Viewed 18 August 2009, retrieved from EBSCOhost.
Mathonnet G, Lachance S, Alaoui-Jamali M, Drobetsky EA, 2004. ‘Expression of hepatitis B virus X oncoprotein inhibits transcription-coupled nucleotide excision repair in human cells’. Mutat Res. Volume 554, pp. 305–318. Viewed 18 August 2009, retrieved from EBSCOhost.
Ming L, Thorgeirsson SS, Gail MH, Lu P, Harris CC, Wang N et al, 2002. ‘Dominant role of hepatitis B virus qand cofactor role of aflatoxin in hepatocarcinogenesis in Qidong, China’. Hepatology. Volume 36, pp. 1214–1220. Viewed 18 August 2009, retrieved from EBSCOhost.
Montalto G, Cervello M, Giannitrapani L, Dantona F, Terranova A, Castagnetta LA, 2002. ‘Epidemiology, risk factors, and natural history of hepatocellular carcinoma’. New York Academy of Science. Volume 963, pp.13-2. Viewed 18 August 2009, retrieved from EBSCOhost.
Parkin DM, Pisani P, Ferlay J, 1999. ‘Estimates of the worldwide incidence of 25 major cancers in 1990. International journal of Cancer. Volume 80, pp. 827-841. Viewed 18 August 2009, retrieved from EBSCOhost.
Seeff LB, Hoofnagle JH, 2006. ‘Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity’. Oncogene. Volume 25, pp. 3771-3777. Viewed 18 August 2009, retrieved from EBSCOhost.
Tang H, Oishi N, Kaneko S, Murakami S, 2006. ‘Molecular functions and biological roles of hepatitis B virus x protein’. Cancer Science. Volume 97, pp. 977–983. Viewed 18 August 2009, retrieved from EBSCOhost.
World Health Organization, 2009. Mortality database. <http://www.who.int/whosis/en>. Viewed 18 August 2009.
Comment