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Liver Functions And Diseases

Liver is a vital organ, which has regenerative property. Liver functions include metabolism, digestion, storage, synthesis and release of vitamins, carbohydrates, proteins and lipids. It also detoxifies and inactivates endogenous and exogenous substances, including toxins and metals. Liver disease is now the fifth most dominant cause of dying after heart disease, stroke, chest disease and cancer, according to UK national statistics, http://www.statistics.gov.uk/. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide, accounting for about 80% of liver cancers and approximately 500,000 deaths annually (Venook et al 2010, http://www.cancer.org/cancer/livercancer/detailedguide/ liver-cancer-what-is-liver-cancer). More than two-thirds of new, worldwide liver cancer cases happen in Asian countries (http://www.pfizer.com/files/products/cancer_in_asia.pdf), and in China alone, an estimated 383,203 deaths in 2012 were attributed to liver cancer (http://globocan.iarc.fr/Pages/fact_sheets_population.aspx). Estimated numbers of HBV and HCV infected subjects worldwide are 370 and 130 million subjects, respectively, and of the 40 million identified HIV positive subjects, 3 million are co-infected with HBV and 4.5 million with HCV (Alter, 2006). Liver cancer incidence and mortality rates are especially high among Asian American men, most notably Vietnamese men (Miller et al 1996). The age-standardized death rate due to liver disease in India is 23.6 per 100,000 individuals according to WHO, 2011 (http://www.worldlifeexpectancy.com/cause-of-death/liver-disease/by-country/). Liver fibrosis is the 9th leading cause of death in the world. The precise prevalence of cirrhosis worldwide is unknown. However, it is more prevalent in the USA followed by Europe, and the numbers are still higher in most Asian and African countries where chronic viral hepatitis B or C are frequent. Since compensated cirrhosis often goes undetected for extended periods of time, a reasonable idea is that up to 1% of populations may have histologically cirrhosis. People with non-alcoholic fatty liver disease ranges from 9 to 36.9% in different parts of the world (Omagari et al 2002, Hilden et al 1977, Shen et al 2003).
The liver is bombarded with mechanical, chemical and pathological insults throughout life. There are more than 100 types of liver diseases in the world which are caused due to viral infection (Hepatitis A, B, and C), alcohol consumption, obesity, genetics, autoimmune diseases, drugs, toxins and cancer. The first sign of liver damage is the formation of scarring and the first stage of liver scarring is fibrosis. Liver fibrosis is main causative factor underlying complications associated with liver pathologies. Liver fibrosis results from changes to cell structure and function, disrupting the normal architecture of the liver and healthy cells are replaced by scar tissue. Over a period of time, this condition leads to the development of liver cirrhosis. Cirrhosis of the liver is a predisposing factor for the development of hepatocellular carcinoma (Bataller and Brenner, 2005).
Liver cirrhosis is one of the diseases of the liver, which is caused by different reasons like alcohol excess, chronic viral hepatitis, drugs and chemicals, etc. Cirrhosis is a condition of severe damage to the liver that impairs its ability to function normally. It causes the formation of scar tissue. This scarring distorts the normal structure, functions and re-growth of liver cells.
The most common types of liver pathologies include
1. Hepatitis – is a condition where liver inflammation is caused due to various viruses (A, B and C), liver toxins such as alcohol, autoimmunity and hereditary conditions. This condition ultimately ends up in fibrosis.
2. Over consumption of alcohol leads to alcoholic liver disease, fatty liver disease, alcoholic hepatitis, and cirrhosis.
3. Non-alcoholic fatty liver disease includes a range of diseases associated with obesity and metabolic syndrome.
4. Hereditary diseases include hemochromatosis, Wilson’s disease, alpha 1-antitrypsin deficiency, glycogen storage disease type II and Gilberts syndrome.
5. Portal hypertension is caused due to high blood pressure in the portal vein of the liver and the causes include liver cirrhosis, fibrosis and hepatic vein thrombosis.
The key factor in all the above conditions involves activation and proliferation of hepatic stellate cells (HSC) and their transformation into myofibroblasts that results in mild/moderate/severe form of liver damage, inflammation, fibrosis, cirrhosis and might lead to liver cancer. Therefore, HSC is an important target for antifibrotic therapy.
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Therapeutic management of liver diseases is difficult with conventional antifibrotic and anti-inflammatory drugs currently on the market, because they either lack efficacy or cause too many side-effects.
Antifibrotic agents targeting hepatic stellate cells are considered as a promising strategy to increase their therapeutic potential.
REFERENCES
1. Venook AP, Papandreou C, Furuse J, de Guevara LL. The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist. 2010; 15(Suppl 4):5–13.
2. Alter, MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006;44:S6-S9.
3. Miller, BA.; Kolonel, L.; Bernstein, L.; Young, JL.; Swanson, GM.; West, DW., et al. Racial/ethnic cancer patterns in the United States 1988–1992. Bethesda: National Cancer Institute; 1996.
4. Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H, et al. (2002). “Fatty liver in non-alcoholic, non overweight Japanese adults: incidence and clinical characteristics”. J Gastroenterol Hepatol: 1098–1105.
5. Hilden M, Christoffersen P, Juhl E, Dalgaard JB (1977). “Liver histology in a ‘normal’ population—examinations of 503 consecutive fatal traffic casualties”. Scand J Gastroenterol 12 (5): 593–7.
6. Shen L, Fan JG, Shao Y, Zeng MD, Wang JR, Luo GH, et al. (2003). “Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey”. World J Gastroenterol 9: 1106–10.
7. Bataller R, Brenner DA. Liver fibrosis. J Clin Invest. 2005 Feb;115(2):209-18.
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