Liver disease (also called hepatic disease) is a type of damage to or disease of the liver.
Associated medical conditions (types)
Primary biliary cirrhosis
There are more than a hundred different kinds of liver disease. Symptoms may include jaundice and weight loss. These are some of the most common:
- Fascioliasis, a parasitic infection of liver caused by a Liver fluke of the Fasciola genus, mostly the Fasciola hepatica.
- Hepatitis, inflammation of the liver, is caused by various viruses (viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity (autoimmune hepatitis) or hereditary conditions.
- Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, and cirrhosis. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.
- Fatty liver disease (hepatic steatosis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells.Non-alcoholic fatty liver disease is a spectrum of disease associated with obesity and metabolic syndrome.
- Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of iron in the body, and Wilson's disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency  and glycogen storage disease type II.
- In transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative and/or cardiopathic effects. Liver transplantation can give a curative treatment option.
- Gilbert's syndrome, a genetic disorder of bilirubin metabolism found in a small percent of the population, can cause mild jaundice.
- Cirrhosis is the formation of fibrous tissue (fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic liver failure.
- Primary liver cancer most commonly manifests as hepatocellular carcinoma and/or cholangiocarcinoma; rarer forms include angiosarcoma and hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)
- Primary biliary cirrhosis is a serious autoimmune disease of the bile capillaries.
- Primary sclerosing cholangitis is a serious chronic inflammatory disease of the bile duct, which is believed to be autoimmune in origin.
- Budd-Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein.
Liver disease can occur through several mechanisms.
One general mechanism, increased DNA damage, is shared by some of the major causes of liver disease. These major causes include infection by hepatitis B virus or hepatitis C virus, alcohol abuse, and obesity.
Viral infection by hepatitis B virus (HBV) or hepatitis C virus (HCV) causes an increase of reactive oxygen species (ROS). The increase in intracellular ROS is about 10,000-fold upon chronic HBV infection and 100,000-fold after HCV infection. This increase in ROS causes inflammation and further increase in ROS. ROS cause more than 20 types of DNA damage. Oxidative DNA damage is mutagenic and also causes epigenetic alterations at the sites of DNA repair.Epigenetic alterations and mutations affect the cellular machinery that may cause the cell to replicate at a higher rate and/or result in the cell avoiding apoptosis, and thus contribute to liver disease. By the time accumulating epigenetic and mutational changes eventually cause hepatocellular carcinoma, epigenetic alterations appear to have an even larger role in carcinogenesis than mutations. Only one gene, TP53, is mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters (repressing gene expression) in more than 20% of liver cancers.
Alcohol consumption in excess causes a build-up of acetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress. In addition, activation of neutrophils in alcoholic liver disease contributes to the pathogenesis of hepatocellular damage by releasing reactive oxygen species (which can damage DNA). The level of oxidative stress and acetaldehyde-induced DNA adducts due to alcohol consumption does not appear sufficient to cause increased mutagenesis. However, as reviewed by Nishida et al., alcohol exposure, causing oxidative DNA damage (which is repairable), can result in epigenetic alterations at the sites of DNA repair. Alcohol-induced epigenetic alterations of gene expression appear to lead to liver injury and ultimately carcinoma.
Obesity is associated with higher risk of primary liver cancer. As shown with mice, obese mice are prone to liver cancer, likely due to two factors. Obese mice have increased pro-inflammatory cytokines. Obese mice also have higher levels of deoxycholic acid (DCA), a product of bile acid alteration by certain gut microbes, and these microbes are increased with obesity. The excess DCA causes DNA damage and inflammation in the liver, which, in turn, can lead to liver cancer.
Other relevant aspects
A common form of liver disease is viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by HBV DNA, but testing for HBsAg is negative. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the liver's cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3-10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma.
According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter.
A number of liver function tests (LFTs) are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins, serum albumin, serum globulin, alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.
Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to examine the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography may reduce the need for biopsy in some situations.
Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:
- By using steroid-based drugs in autoimmune hepatitis.
- Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis.
- Wilson's disease, a condition where copper builds up in the body, can be managed with drugs which bind copper allowing it to be passed from your body in urine.
- In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid (URSO, also referred to as UDCA) may be given.
- ^ a b "Liver Diseases: MedlinePlus". www.nlm.nih.gov. Retrieved .
- ^ a b "Liver function tests: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Liver disease - NHS Choices". www.nhs.uk. Retrieved .
- ^ "CDC - Fasciola". www.cdc.gov. Retrieved .
- ^ "Hepatitis: MedlinePlus". www.nlm.nih.gov. Retrieved .
- ^ "Alcoholic liver disease: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Hepatic steatosis". Retrieved .
- ^ "Non-alcoholic fatty liver disease - NHS Choices". www.nhs.uk. Retrieved .
- ^ "Hemochromatosis: MedlinePlus". www.nlm.nih.gov. Retrieved .
- ^ "Alpha-1 Antitrypsin Deficiency: MedlinePlus". www.nlm.nih.gov. Retrieved .
- ^ Leslie, Nancy; Tinkle, Brad T. (1993). Pagon, Roberta A.; Adam, Margaret P.; Ardinger, Holly H.; Wallace, Stephanie E.; Amemiya, Anne; Bean, Lora JH; Bird, Thomas D.; Dolan, Cynthia R.; Fong, Chin-To, eds. Glycogen Storage Disease Type II (Pompe Disease). Seattle (WA): University of Washington, Seattle. PMID 20301438.
- ^ "Transthyretin amyloidosis". Genetics Home Reference. Retrieved .
- ^ "Gilbert syndrome". Genetics Home Reference. Retrieved .
- ^ "Cirrhosis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Liver cancer - Hepatocellular carcinoma: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Primary biliary cirrhosis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Sclerosing cholangitis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Hepatic vein obstruction (Budd-Chiari): MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved .
- ^ "Chronic Liver Disease/Cirrhosis | Johns Hopkins Medicine Health Library".
- ^ a b Ivanov AV, Valuev-Elliston VT, Tyurina DA, Ivanova ON, Kochetkov SN, Bartosch B, Isaguliants MG (2017). "Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis". Oncotarget. 8 (3): 3895-3932. doi:10.18632/oncotarget.13904. PMC 5354803 . PMID 27965466.
- ^ Yu Y, Cui Y, Niedernhofer LJ, Wang Y (2016). "Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage". Chem. Res. Toxicol. 29 (12): 2008-2039. doi:10.1021/acs.chemrestox.6b00265. PMC 5614522 . PMID 27989142.
- ^ Dizdaroglu M (2012). "Oxidatively induced DNA damage: mechanisms, repair and disease". Cancer Lett. 327 (1-2): 26-47. doi:10.1016/j.canlet.2012.01.016. PMID 22293091.
- ^ a b Nishida N, Kudo M (2013). "Oxidative stress and epigenetic instability in human hepatocarcinogenesis". Dig Dis. 31 (5-6): 447-53. doi:10.1159/000355243. PMID 24281019.
- ^ Shibata T, Aburatani H (2014). "Exploration of liver cancer genomes". Nat Rev Gastroenterol Hepatol. 11 (6): 340-9. doi:10.1038/nrgastro.2014.6. PMID 24473361.
- ^ Ozen C, Yildiz G, Dagcan AT, Cevik D, Ors A, Keles U, Topel H, Ozturk M (2013). "Genetics and epigenetics of liver cancer". N Biotechnol. 30 (4): 381-4. doi:10.1016/j.nbt.2013.01.007. PMID 23392071.
- ^ Yu HS, Oyama T, Isse T, Kitagawa K, Pham TT, Tanaka M, Kawamoto T (2010). "Formation of acetaldehyde-derived DNA adducts due to alcohol exposure". Chem. Biol. Interact. 188 (3): 367-75. doi:10.1016/j.cbi.2010.08.005. PMID 20813101.
- ^ Lee SM, Kim-Ha J, Choi WY, Lee J, Kim D, Lee J, Choi E, Kim YJ (2016). "Interplay of genetic and epigenetic alterations in hepatocellular carcinoma". Epigenomics. 8 (7): 993-1005. doi:10.2217/epi-2016-0027. PMID 27411963.
- ^ "Drinking alcohol causes cancer by 'damaging DNA' - Independent.ie".
- ^ a b Wang HJ, Gao B, Zakhari S, Nagy LE (2012). "Inflammation in alcoholic liver disease". Annu. Rev. Nutr. 32: 343-68. doi:10.1146/annurev-nutr-072610-145138. PMC 3670145 . PMID 22524187.
- ^ Shukla SD, Lim RW (2013). "Epigenetic effects of ethanol on the liver and gastrointestinal system". Alcohol Res. 35 (1): 47-55. PMC 3860425 . PMID 24313164.
- ^ Aleksandrova K, Stelmach-Mardas M, Schlesinger S (2016). "Obesity and Liver Cancer". Recent Results Cancer Res. 208: 177-198. doi:10.1007/978-3-319-42542-9_10. PMID 27909908.
- ^ "Gut Bugs Could Explain Obesity-Cancer Link | Science | AAAS".
- ^ Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ (September 2014). "Vertical transmission of hepatitis C virus: systematic review and meta-analysis". Clinical Infectious Diseases. 59 (6): 765-73. doi:10.1093/cid/ciu447. PMC 4144266 . PMID 24928290.
- ^ Komatsu H (July 2014). "Hepatitis B virus: where do we stand and what is the next step for eradication?". World Journal of Gastroenterology. 20 (27): 8998-9016. doi:10.3748/wjg.v20.i27.8998 (inactive 2017-08-15). PMC 4112872 . PMID 25083074.
- ^ "Hepatitis B and C: ways to promote and offer testing to people at increased risk of infection | Guidance and guidelines | NICE". www.nice.org.uk. Retrieved .
- ^ Samal J, Kandpal M, Vivekanandan P (January 2012). "Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection". Clinical Microbiology Reviews. 25 (1): 142-163. doi:10.1128/CMR.00018-11. PMC 3255968 . PMID 22232374.
- ^ Suk KT, Kim MY, Baik SK (September 2014). "Alcoholic liver disease: treatment". World Journal of Gastroenterology. 20 (36): 12934-44. doi:10.3748/wjg.v20.i36.12934. PMC 4177474 . PMID 25278689.
- ^ a b c Williams JA, Manley S, Ding WX (September 2014). "New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases". World Journal of Gastroenterology. 20 (36): 12908-33. doi:10.3748/wjg.v20.i36.12908. PMC 4177473 . PMID 25278688.
- ^ Tilg, Herbert; Cani, Patrice D.; Mayer, Emeran A. (1 December 2016). "Gut microbiome and liver diseases". Gut. 65 (12): 2035-2044. doi:10.1136/gutjnl-2016-312729. ISSN 1468-3288. PMID 27802157. Retrieved 2016.
- ^ Longo, Dan L.; Tapper, Elliot B.; Lok, Anna S.-F. (24 August 2017). "Use of Liver Imaging and Biopsy in Clinical Practice". New England Journal of Medicine. 377 (8): 756-768. doi:10.1056/NEJMra1610570. PMID 28834467.
- ^ De Clercq, Erik; Férir, Geoffrey; Kaptein, Suzanne; Neyts, Johan (2010). "Antiviral Treatment of Chronic Hepatitis B Virus (HBV) Infections+". Viruses. 2 (6): 1279-1305. doi:10.3390/v2061279. ISSN 1999-4915. PMC 3185710 . PMID 21994680.
- ^ Hirschfield, Gideon M.; Heathcote, E. Jenny (2011-12-02). Autoimmune Hepatitis: A Guide for Practicing Clinicians. Springer Science & Business Media. ISBN 9781607615699.
- ^ "Phlebotomy Treatment | Treatment and Management | Training & Education | Hemochromatosis (Iron Storage Disease) | NCBDDD | CDC". www.cdc.gov. Retrieved .
- ^ "Wilson Disease". www.niddk.nih.gov. Retrieved .
- ^ Suchy, Frederick J.; Sokol, Ronald J.; Balistreri, William F. (2014-02-20). Liver Disease in Children. Cambridge University Press. ISBN 9781107729094.
- ^ "Ursodeoxycholic acid for liver disease related to cystic fibrosis | Cochrane". www.cochrane.org. Retrieved .