Liver transplantation

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Intervention: Liver transplantation
Human liver
ICD-10 code:
ICD-9 code:	50.5
MeSH	D016031
Other codes:

Liver transplantation or hepatic transplantation is the replacement of a diseased liver with a healthy liver allograft. The most commonly used technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic location as the original liver. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. It is also one of the most expensive treatments in modern medicine.

Contents [hide] 1 History 2 Indications 3 Techniques 4 Immunosuppressive management 5 Graft rejection 6 Results 7 Living donor transplantation 7.1 Liver donor requirements 7.2 Complications 7.3 Pediatric transplantation 7.4 Benefits 7.5 Screening for donors 7.6 Economic aspect 8 Controversy over eligibility for alcoholics 9 References 10 Further reading 11 External links

[edit] History

The first human liver transplant was performed in 1963 by a surgical team led by Dr. Thomas Starzl^[1] of Denver, Colorado, United States. Dr. Starzl performed several additional transplants over the next few years before the first short-term success was achieved in 1967 with the first one-year survival post transplantation. Despite the development of viable surgical techniques, liver transplantation remained experimental through the 1970s, with one year patient survival in the vicinity of 25%.^[2] The introduction of ciclosporin by Sir Roy Calne markedly improved patient outcomes, and the 1980s saw recognition of liver transplantation as a standard clinical treatment for both adult and pediatric patients with appropriate indications. Liver transplantation is now performed at over one hundred centres in the USA, as well as numerous centres in Europe and elsewhere. One year patient survival is 80-85%, and outcomes continue to improve, although liver transplantation remains a formidable procedure with frequent complications. Unfortunately, the supply of liver allografts from non-living donors is far short of the number of potential recipients, a reality that has spurred the development of living donor liver transplantation.

[edit] Indications

Liver transplantation is potentially applicable to any acute or chronic condition resulting in irreversible liver dysfunction, provided that the recipient does not have other conditions that will preclude a successful transplant. Metastatic cancer outside liver, active drug or alcohol abuse and active septic infections are absolute contraindications. While infection with HIV was once considered an absolute contraindication, this has been changing recently. Advanced age and serious heart, pulmonary or other disease may also prevent transplantation (relative contraindications). Most liver transplants are performed for chronic liver diseases that lead to irreversible scarring of the liver, or cirrhosis of the liver. Another cause is cryptogenic liver disease. Some centers use the Milan criteria to select patients for liver transplantation.

[edit] Techniques

Before transplantation liver support therapy might be indicated (bridging-to-transplantation). Artificial liver support like liver dialysis or bioartificial liver support concepts are currently under preclinical and clinical evaluation. Virtually all liver transplants are done in an orthotopic fashion, that is the native liver is removed and the new liver is placed in the same anatomic location. The transplant operation can be conceptualized as consisting of the hepatectomy (liver removal) phase, the anhepatic (no liver) phase, and the postimplantation phase. The operation is done through a large incision in the upper abdomen. The hepatectomy involves division of all ligamentous attachments to the liver, as well as the common bile duct, hepatic artery, hepatic vein and portal vein. Usually, the retrohepatic portion of the inferior vena cava is removed along with the liver, although an alternative technique preserves the recipient's vena cava ("piggyback" technique).

The donor's blood in the liver will be replaced by an ice-cold organ storage solution, such as UW (Viaspan) or HTK until the allograft liver is implanted. Implantation involves anastomoses (connections) of the inferior vena cava, portal vein, and hepatic artery. After blood flow is restored to the new liver, the biliary (bile duct) anastomosis is constructed, either to the recipient's own bile duct or to the small intestine. The surgery usually takes between five and six hours, but may be longer or shorter due to the difficulty of the operation and the experience of the surgeon.

The large majority of liver transplants use the entire liver from a non-living donor for the transplant, particularly for adult recipients. A major advance in pediatric liver transplantation was the development of reduced size liver transplantation, in which a portion of an adult liver is used for an infant or small child. Further developments in this area included split liver transplantation, in which one liver is used for transplants for two recipients, and living donor liver transplantation, in which a portion of a healthy person's liver is removed and used as the allograft. Living donor liver transplantation for pediatric recipients involves removal of approximately 20% of the liver (Couinaud segments 2 and 3).

[edit] Immunosuppressive management

Like most other allografts, a liver transplant will be rejected by the recipient unless immunosuppressive drugs are used. The immunosuppressive regimens for all solid organ transplants are fairly similar, and a variety of agents are now available. Most liver transplant recipients receive corticosteroids plus a calcinuerin inhibitor such as tacrolimus or ciclosporin plus an antimetabolite such as Mycophenolate Mofetil.

Liver transplantation is unique in that the risk of chronic rejection also decreases over time, although recipients need to take immunosuppressive medication for the rest of their lives. It is theorized that the liver may play a yet-unknown role in the maturation of certain cells pertaining to the immune system. There is at least one study by Dr. Starzl's team at the University of Pittsburgh which consisted of bone marrow biopsies taken from such patients which demonstrate genotypic chimerism in the bone marrow of liver transplant recipients.

[edit] Graft rejection

After a liver transplantation, there are three types of graft rejection that may occur. They include hyperacute rejection, acute rejection and chronic rejection. Hyperacute rejection is caused by preformed anti-donor antibodies. It is characterized by the binding of these antibodies to antigens on vascular endothelial cells. Complement activation is involved and the effect is usually profound. Hyperacute rejection happens within minutes to hours after the transplant procedure. Unlike hyperacute rejection, which is B cell mediated, acute rejection is mediated by T cells. It involves direct cytotoxicity and cytokine mediated pathways. Acute rejection is the most common and the primary target of immunosuppressive agents. Acute rejection is usually seen within days or weeks of the transplant. Chronic rejection is the presence of any sign and symptom of rejection after 1 year. The cause of chronic rejection is still unknown but an acute rejection is a strong predictor of chronic rejections. Liver rejection may happen anytime after the transplant. Lab findings of a liver rejection include abnormal AST, ALT, GGT and liver function values such as prothrombin time, ammonia level, bilirubin level, albumin concentration, and blood glucose. Physical findings include encephalopathy, jaundice, bruising and bleeding tendency. Other nonspecific presentation are malaise, anorexia, muscle ache, low fever, slight increase in white blood count and graft tender.

[edit] Results

Prognosis is quite good. However, those with certain illnesses may differ.^[3] There is no exact model to predict survival rates; however, those with transplant have a 58% chance of surviving 15 years.^[4] Failure from the new liver occurs in 10% to 15% of all cases. These percentages are contributed to by many complications. Early graft failure is probably due to preexisting disease of the donated organ. Others include technical flaws during surgery such as revascularization that may lead to a nonfunctioning graft.

[edit] Living donor transplantation

Living donor liver transplantation (LDLT) has emerged in recent decades as a critical surgical option for patients with end stage liver disease, such as cirrhosis and/or hepatocellular carcinoma often attributable to one or more of the following: long-term alcohol abuse, long-term untreated Hepatitis C infection, long-term untreated Hepatitis B infection. The concept of LDLT is based on (1) the remarkable regenerative capacities of the human liver and (2) the widespread shortage of cadaveric livers for patients awaiting transplant. In LDLT, a piece of healthy liver is surgically removed from a living person and transplanted into a recipient, immediately after the recipient’s diseased liver has been entirely removed.

Historically, LDLT began as a means for parents of children with severe liver disease to donate a portion of their healthy liver to replace their child's entire damaged liver. The first report of successful LDLT was by Dr. Christoph Broelsch at the University of Chicago Medical Center in November 1989, when two-year-old Alyssa Smith received a portion of her mother's liver.^[5] Surgeons eventually realized that adult-to-adult LDLT was also possible, and now the practice is common in a few reputable medical institutes. It is considered more technically demanding than even standard, cadaveric donor liver transplantation, and also poses the ethical problems underlying the indication of a major surgical operation (hepatectomy) on a healthy human being. In various case series the risk of complications in the donor is around 10%, and very occasionally a second operation is needed. Common problems are biliary fistula, gastric stasis and infections; they are more common after removal of the right lobe of the liver. Death after LDLT has been reported at 0% (Japan), 0.3% (USA) and [6]

In a typical adult recipient LDLT, 55 to 70% of the liver (the right lobe) is removed from a healthy living donor. The donor's liver will regenerate approaching 100% function within 4–6 weeks and will almost reach full volumetric size with recapitulation of the normal structure soon thereafter. It may be possible to remove up to 70% of the liver from a healthy living donor without harm in most cases. The transplanted portion will reach full function and the appropriate size in the recipient as well, although it will take longer than for the donor. [1]

Living donors are faced with risks and/or complications after the surgery. Blood clots and biliary problems have the possibility of arising in the donor post-op, but these issues are remedied fairly easily. Although death is a risk that a living donor must be willing to accept prior to the surgery, the mortality rate of living donors in the United States is low. The LDLT donor's immune system does diminish as a result of the liver regenerating, so certain foods which would normally cause an upset stomach could cause serious illness.

[edit] Liver donor requirements

Any member of the family, parent, sibling, child, spouse or a volunteer can donate their liver. The criteria for a liver donation include:

• Being in good health
• Having a blood type that matches or is compatible with the recipient's
• Having a charitable desire of donation without financial motivation
• Being between 18 and 60 years old
• Being of similar or bigger size than the recipient
• Before one becomes a living donor, the donor has to undergo testing to ensure that the individual is physically fit. Sometimes CT scans or MRI are done to image the liver. In most cases, the work up is done in 2-3 weeks ^[7]

[edit] Complications

Living donor surgery is done at a major center. Very few individuals require any blood transfusions during or after surgery. Even though the procedure is very safe, all potential donors should know there is a 0-5 to 1 percent chance of death. Other risk of donating a liver include bleeding, infection, painful incision, possibility of blood clots and a prolonged recovery.^[8] The vast majority of donors enjoy complete and full recovery within 2-3 months.

[edit] Pediatric transplantation

In children living liver donor transplantation have become very accepted. The accessibility of adult parents who want to donate a piece of the liver for their children/infants has reduced the number of children who would have otherwise died waiting for a transplant. Having a parent as a donor also has made it a lot easier for children - because both patients are in the same hospital and can help boost each other's morale.^[9]

[edit] Benefits

The advantages of living liver donor transplantation has several benefits over cadaveric donor transplantation including:

• Transplant can be done on an elective basis because the donor is readily available
• There are less possibilities for complications and death while waiting for a cadaveric organ donor
• Because of donor shortages, UNOS has limited the cadaveric organ allocation to foreigners who seek medical help in the USA. However, with the availability of living donor transplantation, this will now allow foreigners a new opportunity to seek medical care in the USA

[edit] Screening for donors

The majority of liver transplantation centers in the USA have a superb record on long term survival. Living donor transplantation is a multidisciplinary approach. All living liver donors undergo medical evaluation. Every hospital which performs transplant have dedicated nurses that provide specific information about the procedure and answer questions that families may have. During the evaluation process, confidentially is assured on the potential donor. Every effort is made to ensure that organ donation is not made by coercion from other family members. The transplant team provides both the donor and family thorough counseling and support which continues until full recovery is made. ^[10]

All donors are assessed medically to ensure that they can undergo the surgery. Blood type of the donor and recipient must be compatible but not always identical. Other things assessed prior to surgery include the anatomy of the donor liver. However, even with mild variations in blood vessels and bile duct, surgeons today are able to perform transplantation without problems. The most important criteria for a living liver donor is to be in excellent health. ^[11]

[edit] Economic aspect

The medical expenses including work up, surgery and post operative recovery period are usually covered by the recipient's health insurance plans in most cases. There are also programs like the National Living Donor Assistance Center which provides financial assistance to help cover the cost of travel, accommodation and other expenses. This program also pays for postoperative trips including expenses for accompanying individuals. ^[12]

[edit] Controversy over eligibility for alcoholics

The high incidence of liver transplants given to those with alcoholic cirrhosis has led to a recurring controversy regarding the eligibility of such patients for liver transplant. The controversy stems from the view of alcoholism as a self-inflicted disease and the perception that those with alcohol-induced damage are depriving other patients who could be considered more deserving.^[13]

[edit] References

1. ^ STARZL T, MARCHIORO T, VONKAULLA K, HERMANN G, BRITTAIN R, WADDELL W. "Homotransplantation Of The Liver In Humans". Surg Gynecol Obstet 117: 659–76. PMID 14100514.
2. ^ Starzl TE, Klintmalm GB, Porter KA, Iwatsuki S, Schroter GP. (1981). "Liver transplantation with use of cyclosporin A and prednisone". New England Journal of Medicine 305: 266–269. PMID 7017414.
3. ^ http://www.innovations-report.com/html/reports/medicine_health/report-22829.html
4. ^ https://www.uktransplant.org.uk/ukt/statistics/presentations/pdfs/april_05/liver_life_expectancy.pdf
5. ^ http://www.uchicagokidshospital.org/specialties/transplant/patient-stories/alyssa-liver.html
6. ^ Umeshita K, Fujiwara K, Kiyosawa K, et al. (August 2003). "Operative morbidity of living liver donors in Japan". Lancet 362 (9385): 687–90. doi:10.1016/S0140-6736(03)14230-4. PMID 12957090.
7. ^ Who can be a Donor? - University of Maryland Medical Center, Retrieved on 2010-01-20.
8. ^ Liver Transplant, Retrieved on 2010-01-20.
9. ^ hat I need to know about Liver Transplantation, National Digestive Diseases Information Clearinghouse (NDDIC), Retrieved on 2010-01-20.
10. ^ Liver Donor: All you need to know, Retrieved on 2010-01-20.
11. ^ Liver Transplant Program And Center for Liver Disease, University of Southern California Department of Surgery, Retrieved on 2010-01-20.
12. ^ Liver Transplants, University of California, San Francisco, Retrieved on 2010-01-20.
13. ^ http://www.psychologytoday.com/blog/mouse-man/200902/do-alcoholics-deserve-liver-transplants

[edit] Further reading

• Eghtesad B, Kadry Z, Fung J (2005). "Technical considerations in liver transplantation: what a hepatologist needs to know (and every surgeon should practice)". Liver Transpl 11 (8): 861–71. doi:10.1002/lt.20529. PMID 16035067.
• Adam R, McMaster P, O'Grady JG, Castaing D, Klempnauer JL, Jamieson N, Neuhaus P, Lerut J, Salizzoni M, Pollard S, Muhlbacher F, Rogiers X, Garcia Valdecasas JC, Berenguer J, Jaeck D, Moreno Gonzalez E (2003). "Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry". Liver Transpl 9 (12): 1231–43. doi:10.1016/j.lts.2003.09.018. PMID 14625822.
• Reddy S, Zilvetti M, Brockmann J, McLaren A, Friend P (2004). "Liver transplantation from non-heart-beating donors: current status and future prospects". Liver Transpl 10 (10): 1223–32. doi:10.1002/lt.20268. PMID 15376341.
• Tuttle-Newhall JE, Collins BH, Desai DM, Kuo PC, Heneghan MA (2005). "The current status of living donor liver transplantation". Curr Probl Surg 42 (3): 144–83. doi:10.1067/j.cpsurg.2004.12.003. PMID 15859440.
• Martinez OM, Rosen HR (2005). "Basic concepts in transplant immunology". Liver Transpl 11 (4): 370–81. doi:10.1002/lt.20406. PMID 15776458.
• Krahn LE, DiMartini A (2005). "Psychiatric and psychosocial aspects of liver transplantation". Liver Transpl 11 (10): 1157–68. doi:10.1002/lt.20578. PMID 16184540.
• Nadalin S, Malagò M, et al. Current trends in live liver donation. Transpl. Int. 2007;20:312-30.
• Vohra V. Liver transplantation in India. Int Anesthesiol Clin. 2006;44:137-49.
• Strong RW. Living-donor liver transplantation: an overview. J Hepatobiliary Pancreat Surg. 2006;13:370-7.
• Fan ST. Live donor liver transplantation in adults. Transplantation. 2006;82:723-32.

[edit] External links

• Official organ sharing network of U.S.
• Official organ procurement center of the U.S.
• American Liver Foundation: Comprehensive information about Hepatitis C, Liver Transplant and other liver diseases, including links to chapters for finding local resources
• Management of HBV Infection in Liver Transplantation Patients
• Management of HCV Infection and Liver Transplantation
• Antiviral therapy of HCV in the cirrhotic and transplant candidate
• Living Donors Online
• Liver Transplantation Guide and Liver Transplant Surgery in India
• History of pediatric liver transplantation
• ABC Salutaris: Living Donor Liver Transplant
• All You Need to Know about Adult Living Donor Liver Transplantation
• Children's Liver Disease Foundation

[show] v • d • e Organ transplantation Types Autotransplantation · Allotransplantation · Xenotransplantation Organs and tissues Bone · Bone marrow · Corneal · Face · Hand · Head · Heart · Heart-lung · Kidney · Liver · Lung · Pancreas · Penis · Skin · Spleen · Uterus Related topics Biomedical tissue · Cellular memory · Edmonton protocol · Eye bank · Graft-versus-host disease · Immunosuppressive drugs · Islet cell transplantation · Implants · Living donor liver transplantation · Lung allocation score · Machine perfusion · Medical grafting · Non-heart beating donation · Organ donation · Post-transplant lymphoproliferative disorder · Repugnant market · Total body irradiation · Transplant rejection · Transplantation medicine Organizations Halachic Organ Donor Society · Human Tissue Authority · National Marrow Donor Program · United Network for Organ Sharing · DKMS Americas People Christiaan Barnard · Michael Woodruff · Alexis Carrel · Norman Shumway · Jean-Michel Dubernard · List of notable organ transplant donors and recipients

[show] v • d • e Digestive system surgical and other procedures (ICD-9-CM V3 42-54) Digestive tract Upper GI tract SGs/Esophagus Sialography · Esophagectomy · Impedance-pH monitoring · Esophageal pH monitoring · Esophageal motility study Stomach Gastrostomy (Percutaneous endoscopic gastrostomy) · Gastrectomy (Billroth I, Billroth II, Roux-en-Y) · Bariatric surgery (Gastric bypass surgery, Adjustable gastric band, Sleeve gastrectomy, Vertical banded gastroplasty surgery) · Gastroenterostomy · Hill repair · Nissen fundoplication · Gastropexy · Pyloromyotomy Imaging Endoscopy: Esophagogastroduodenoscopy Upper gastrointestinal series Lower GI tract Small bowel Bariatric surgery (Duodenal switch, Jejunoileal bypass) · Jejunostomy · Ileostomy · Partial ileal bypass surgery Large bowel Colectomy · Colostomy · Appendicectomy · Hartmann's operation Rectum Lower anterior resection · Abdominoperineal resection Anus Anal sphincterotomy · Lateral internal sphincterotomy Imaging Endoscopy: Colonoscopy (Virtual) · Proctoscopy · Sigmoidoscopy · Enteroscopy · Capsule endoscopy Transrectal ultrasonography · Enteroclysis · Small bowel follow-through · Abdominal ultrasonography · Lower gastrointestinal series Stool tests Fecal pH test · Stool guaiac test · Fecal fat test Accessory Liver Hepatectomy · Liver transplantation · Artificial extracorporeal liver support (Liver dialysis, Bioartificial liver devices) Gallbladder, bile duct Cholangiography (Endoscopic retrograde cholangiopancreatography, Percutaneous transhepatic cholangiography, Magnetic resonance cholangiopancreatography) · Cholecystectomy · Cholecystography · Cholescintigraphy · Hepatoportoenterostomy Pancreas Pancreatectomy · Pancreaticoduodenectomy · Pancreas transplantation · Puestow procedure · Frey's procedure Abdominopelvic Peritoneum Paracentesis · Intraperitoneal injection Hernia Herniorrhaphy · Macewen's operation Other Laparotomy M: DIG anat(t,g,p)/phys/devp/cell noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16)

Retrieved from "http://en.wikipedia.org/wiki/Liver_transplantation"

Categories: Gastroenterology | Hepatology | Surgical procedures | Transplantation medicine

Liver

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Jump to: navigation, search

Liver
Liver of a sheep: (1) right lobe, (2) left lobe, (3) caudate lobe, (4) quadrate lobe, (5) hepatic artery and portal vein, (6) hepatic lymph nodes, (7) gall bladder.
Anterior view of the position of the liver (purple) in the human abdomen.
Latin	jecur, iecer
Gray's	subject #250 1188
Vein	hepatic vein, hepatic portal vein
Nerve	celiac ganglia, vagus[1]
Precursor	foregut
MeSH	Liver

For other uses, see Liver (disambiguation).

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion. The liver is necessary for survival; there is currently no way to compensate for the absence of liver function.

This organ plays a major role in metabolism and has a number of functions in the body, including glycogen storage, decomposition of red blood cells, plasma protein synthesis, hormone production, and detoxification. It lies below the diaphragm in the thoracic region of the abdomen. It produces bile, an alkaline compound which aids in digestion, via the emulsification of lipids. It also performs and regulates a wide variety of high-volume biochemical reactions requiring highly specialized tissues, including the synthesis and breakdown of small and complex molecules, many of which are necessary for normal vital functions.^[2]

Medical terms related to the liver often start in hepato- or hepatic from the Greek word for liver, hēpar (ἡπαρ).^[3]

Contents [hide] 1 Anatomy 1.1 Blood flow 1.2 Biliary flow 1.3 Surface anatomy 1.3.1 Peritoneal ligaments 1.3.2 Lobes 1.4 Functional anatomy 1.5 In other animals 2 Physiology 2.1 Synthesis 2.2 Breakdown 2.3 Other functions 3 Diseases of the liver 4 Disease signs 5 Diagnosis 6 Biopsy 7 Regeneration 8 Liver transplantation 9 Development 9.1 Fetal blood supply 10 As food 11 Cultural allusions 12 See also 13 References 14 Further reading 15 External links

[edit] Anatomy

The liver is a reddish brown organ with four lobes of unequal size and shape. A human liver normally weighs between 1.4–1.6 kg (3.1–3.5 lb),^[4] and is a soft, pinkish-brown, triangular organ. It is both the largest internal organ (the skin being the largest organ overall) and the largest gland in the human body.

It is located in the right upper quadrant of the abdominal cavity, resting just below the diaphragm. The liver lies to the right of the stomach and overlies the gallbladder. It is connected to two large blood vessels, one called the hepatic artery and one called the portal vein. The hepatic artery carries blood from the aorta whereas the portal vein carries blood containing digested nutrients from the small intestine and the descending colon. These blood vessels subdivide into capillaries which then lead to a lobule. Each lobule is made up of millions of hepatic cells which are the basic metabolic cells.

[edit] Blood flow

The liver receives a dual blood supply from the hepatic portal vein and hepatic arteries. Supplying approximately 75% of the liver's blood supply, the hepatic portal vein carries venous blood drained from the spleen, gastrointestinal tract, and its associated organs. The hepatic arteries supply arterial blood to the liver, accounting for the remainder of its blood flow. Oxygen is provided from both sources; approximately half of the liver's oxygen demand is met by the hepatic portal vein, and half is met by the hepatic arteries.^[5] Blood flows through the sinusoids and empties into the central vein of each lobule. The central veins coalesce into hepatic veins, which leave the liver and empty into the inferior vena cava.

[edit] Biliary flow

The term biliary tree is derived from the arboreal branches of the bile ducts. The bile produced in the liver is collected in bile canaliculi, which merge to form bile ducts. Within the liver, these ducts are called intrahepatic (within the liver) bile ducts, and once they exit the liver they are considered extrahepatic (outside the liver). The intrahepatic ducts eventually drain into the right and left hepatic ducts, which merge to form the common hepatic duct. The cystic duct from the gallbladder joins with the common hepatic duct to form the common bile duct.

Bile can either drain directly into the duodenum via the common bile duct or be temporarily stored in the gallbladder via the cystic duct. The common bile duct and the pancreatic duct enter the second part of the duodenum together at the ampulla of Vater.

The biliary tree

[edit] Surface anatomy

[edit] Peritoneal ligaments

Apart from a patch where it connects to the diaphragm (the so-called "bare area"), the liver is covered entirely by visceral peritoneum, a thin, double-layered membrane that reduces friction against other organs. The peritoneum folds back on itself to form the falciform ligament and the right and left triangular ligaments.

These "lits" are in no way related to the true anatomic ligaments in joints, and have essentially no functional importance, but they are easily recognizable surface landmarks. An exception to this is the falciform ligament, which attaches the liver to the posterior portion of the anterior body wall.

[edit] Lobes

Traditional gross anatomy divided the liver into four lobes based on surface features. The falciform ligament is visible on the front (anterior side) of the liver. This divides the liver into a left anatomical lobe, and a right anatomical lobe.

If the liver is flipped over, to look at it from behind (the visceral surface), there are two additional lobes between the right and left. These are the caudate lobe (the more superior), and below this the quadrate lobe.

From behind, the lobes are divided up by the ligamentum venosum and ligamentum teres (anything left of these is the left lobe), the transverse fissure (or porta hepatis) divides the caudate from the quadrate lobe, and the right sagittal fossa, which the inferior vena cava runs over, separates these two lobes from the right lobe.

Each of the lobes is made up of lobules; a vein goes from the centre of each lobule which then joins to the hepatic vein to carry blood out from the liver.

On the surface of the lobules there are ducts, veins and arteries that carry fluids to and from them.

[edit] Functional anatomy

Correspondence between anatomic lobes and Couinaud segments

Segment*	Couinaud segments
Caudate	1
Lateral	2, 3
Medial	4a, 4b
Right	5, 6, 7, 8
* or lobe in the case of the caudate lobe. Each number in the list corresponds to one in the table. Caudate Superior subsegment of the lateral segment Inferior subsegment of the lateral segment Superior subsegment of the medial segment Inferior subsegment of the medial segment Inferior subsegment of the anterior segment Inferior subsegment of the posterior segment Superior subsegment of the posterior segment Superior subsegment of the anterior segment

The central area where the common bile duct, hepatic portal vein, and hepatic artery proper enter is the hilum or "porta hepatis". The duct, vein, and artery divide into left and right branches, and the portions of the liver supplied by these branches constitute the functional left and right lobes.

The functional lobes are separated by an imaginary plane joining the gallbladder fossa to the inferior vena cava. The plane separates the liver into the true right and left lobes. The middle hepatic vein also demarcates the true right and left lobes. The right lobe is further divided into an anterior and posterior segment by the right hepatic vein. The left lobe is divided into the medial and lateral segments by the left hepatic vein. The fissure for the ligamentum teres also separates the medial and lateral segments. The medial segment is also called the quadrate lobe. In the widely used Couinaud (or "French") system, the functional lobes are further divided into a total of eight subsegments based on a transverse plane through the bifurcation of the main portal vein. The caudate lobe is a separate structure which receives blood flow from both the right- and left-sided vascular branches.^[6][7]

[edit] In other animals

The liver is found in all vertebrates, and is typically the largest visceral organ. Its form varies considerably in different species, and is largely determined by the shape and arrangement of the surrounding organs. Nonetheless, in most species it is divided into right and left lobes; exceptions to this general rule include snakes, where the shape of the body necessitates a simple cigar-like form. The internal structure of the liver is broadly similar in all vertebrates.^[8]

An organ sometimes referred to as a liver is found associated with the digestive tract of the primitive chordate Amphioxus. However, this is an enzyme secreting gland, not a metabolic organ, and it is unclear how truly homologous it is to the vertebrate liver.^[8]

[edit] Physiology

The various functions of the liver are carried out by the liver cells or hepatocytes. Currently, there is no artificial organ or device capable of emulating all the functions of the liver. Some functions can be emulated by liver dialysis, an experimental treatment for liver failure.

[edit] Synthesis

Further information: Proteins produced and secreted by the liver

• A large part of amino acid synthesis
• The liver performs several roles in carbohydrate metabolism:
  • Gluconeogenesis (the synthesis of glucose from certain amino acids, lactate or glycerol). Note that humans and some other mammals cannot synthesize glucose from glycerol.
  • Glycogenolysis (the breakdown of glycogen into glucose)
  • Glycogenesis (the formation of glycogen from glucose)(muscle tissues can also do this)
• The liver is responsible for the mainstay of protein metabolism, synthesis as well as degradation
• The liver also performs several roles in lipid metabolism:
  • Cholesterol synthesis
  • Lipogenesis, the production of triglycerides (fats).
• The liver produces coagulation factors I (fibrinogen), II (prothrombin), V, VII, IX, X and XI, as well as protein C, protein S and antithrombin.
• In the first trimester fetus, the liver is the main site of red blood cell production. By the 32nd week of gestation, the bone marrow has almost completely taken over that task.
• The liver produces and excretes bile (a yellowish liquid) required for emulsifying fats. Some of the bile drains directly into the duodenum, and some is stored in the gallbladder.
• The liver also produces insulin-like growth factor 1 (IGF-1), a polypeptide protein hormone that plays an important role in childhood growth and continues to have anabolic effects in adults.
• The liver is a major site of thrombopoietin production. Thrombopoietin is a glycoprotein hormone that regulates the production of platelets by the bone marrow.

[edit] Breakdown

• The breakdown of insulin and other hormones
• The liver breaks down hemoglobin, creating metabolites that are added to bile as pigment (bilirubin and biliverdin).
• The liver breaks down or modifies toxic substances (e.g., methylation) and most medicinal products in a process called drug metabolism. This sometimes results in toxication, when the metabolite is more toxic than its precursor. Preferably, the toxins are conjugated to avail excretion in bile or urine.
• The liver converts ammonia to urea.

[edit] Other functions

• The liver stores a multitude of substances, including glucose (in the form of glycogen), vitamin A (1–2 years' supply), vitamin D (1–4 months' supply), vitamin B12 (1-3 years' supply), iron, and copper.
• The liver is responsible for immunological effects- the reticuloendothelial system of the liver contains many immunologically active cells, acting as a 'sieve' for antigens carried to it via the portal system.
• The liver produces albumin, the major osmolar component of blood serum.
• The liver synthesizes angiotensinogen, a hormone that is responsible for raising the blood pressure when activated by renin, an enzyme that is released when the kidney senses low blood pressure.

[edit] Diseases of the liver

Main article: Liver disease

Left lobe liver tumor

The liver supports almost every organ in the body and is vital for survival. Because of its strategic location and multidimensional functions, the liver is also prone to many diseases.^[9]

The most common include: Infections such as hepatitis A, B, C, E, alcohol damage, fatty liver, cirrhosis, cancer, drug damage (especially acetaminophen, cancer drugs)

Many diseases of the liver are accompanied by jaundice caused by increased levels of bilirubin in the system. The bilirubin results from the breakup of the haemoglobin of dead red blood cells; normally, the liver removes bilirubin from the blood and excretes it through bile.

There are also many pediatric liver diseases including biliary atresia, alpha-1 antitrypsin deficiency, alagille syndrome, progressive familial intrahepatic cholestasis, and Langerhans cell histiocytosis, to name but a few.

Diseases that interfere with liver function will lead to derangement of these processes. However, the liver has a great capacity to regenerate and has a large reserve capacity. In most cases, the liver only produces symptoms after extensive damage.^[10]

Liver diseases may be diagnosed by liver function tests, for example, by production of acute phase proteins.

[edit] Disease signs

The classic signs of liver damage include the following:

• Pale stools occur when stercobilin, a brown pigment, is absent from the stool. Stercobilin is derived from bilirubin metabolites produced in the liver.
• Dark urine occurs when bilirubin mixes with urine
• Bilirubin when it deposits in skin, causes an intense itch. Itching is the most common complaint by people who have liver failure. Often this itch cannot be relieved by drugs.
• Swelling of the abdomen, ankles and feet occurs because the liver fails to make albumin.
• Excessive fatigue occurs from a generalized loss of nutrients, minerals and vitamins.
• Bruising and easy bleeding are other features of liver disease. The liver makes substances which help prevent bleeding. When liver damage occurs, these substances are no longer present and severe bleeding can occur.^[11]

[edit] Diagnosis

The diagnosis of liver function is made by blood tests. Liver function tests can readily pinpoint the extent of liver damage. If infection is suspected, then other serological tests are done. Sometimes one may require an ultrasound or a CT scan to image the liver.

Physical exam of the liver is not accurate in determining the extent of liver damage. Physical exam can only reveal presence of tenderness or size of liver but in all cases some type of radiological study is required to look at the liver.^[12]

[edit] Biopsy

The ideal way to look at damage to the liver is with a biopsy. A biopsy is not required in all cases but may be necessary when the cause is unknown. The procedure is done at the bedside and only requires local anesthetic. A small thin needle is inserted into the skin just below the rib cage and a biopsy is obtained. The tissue is sent to the laboratory where it is analyzed under a microscope. Sometimes the radiologist may perform a liver biopsy under ultrasound guidance if only a small area is involved.^[13]

[edit] Regeneration

The liver is the only internal human organ capable of natural regeneration of lost tissue; as little as 25% of a liver can regenerate into a whole liver.

This is predominantly due to the hepatocytes re-entering the cell cycle. That is, the hepatocytes go from the quiescent G0 phase to the G1 phase and undergo mitosis. This process is activated by the p75 receptors.^[14] There is also some evidence of bipotential stem cells, called ovalocytes or hepatic oval cells, which are thought to reside in the canals of Hering. These cells can differentiate into either hepatocytes or cholangiocytes, the latter being the cells that line the bile ducts.

The capability for the liver to regenerate itself has been known since at least the times of the ancient Greeks, whose mythology includes a story about Prometheus being chained to a rock in the Caucasus mountain and his liver being partially eaten during the day by an eagle only to "regenerate" in the night.^[15] The story, however, embellishes the speed with which this occurs.

[edit] Liver transplantation

Main article: Liver transplantation

Human liver transplants were first performed by Thomas Starzl in the United States and Roy Calne in Cambridge, England in 1963 and 1965, respectively.

After resection of left lobe liver tumor

Liver transplantation is the only option for those with irreversible liver failure. Most transplants are done for chronic liver diseases leading to cirrhosis, such as chronic hepatitis C, alcoholism, autoimmune hepatitis, and many others. Less commonly, liver transplantation is done for fulminant hepatic failure, in which liver failure occurs over days to weeks.

Liver allografts for transplant usually come from non-living donors who have died from fatal brain injury. Living donor liver transplantation is a technique in which a portion of a living person's liver is removed and used to replace the entire liver of the recipient. This was first performed in 1989 for pediatric liver transplantation. Only 20% of an adult's liver (Couinaud segments 2 and 3) is needed to serve as a liver allograft for an infant or small child.

More recently, adult-to-adult liver transplantation has been done using the donor's right hepatic lobe which amounts to 60% of the liver. Due to the ability of the liver to regenerate, both the donor and recipient end up with normal liver function if all goes well. This procedure is more controversial as it entails performing a much larger operation on the donor, and indeed there have been at least 2 donor deaths out of the first several hundred cases. A recent publication has addressed the problem of donor mortality, and at least 14 cases have been found.^[16] The risk of postoperative complications (and death) is far greater in right-sided operations than that in left-sided operations.

With the recent advances of non-invasive imaging, living liver donors usually have to undergo imaging examinations for liver anatomy to decide if the anatomy is feasible for donation. The evaluation is usually performed by multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI). MDCT is good in vascular anatomy and volumetry. MRI is used for biliary tree anatomy. Donors with very unusual vascular anatomy, which makes them unsuitable for donation, could be screened out to avoid unnecessary operations.

MDCT image. Arterial anatomy contraindicated for liver donation.

MDCT image. Portal venous anatomy contraindicated for liver donation.

MDCT image. 3D image created by MDCT can clearly visualize the liver, measure the liver volume, and plan the dissection plane to facilitate the liver transplantation procedure.

Phase contrast CT image. Contrast is perfusing the right liver but not the left due to a left portal vein thrombus.

[edit] Development

[edit] Fetal blood supply

In the growing fetus, a major source of blood to the liver is the umbilical vein which supplies nutrients to the growing fetus. The umbilical vein enters the abdomen at the umbilicus, and passes upward along the free margin of the falciform ligament of the liver to the inferior surface of the liver. There it joins with the left branch of the portal vein. The ductus venosus carries blood from the left portal vein to the left hepatic vein and then to the inferior vena cava, allowing placental blood to bypass the liver.

In the fetus, the liver develops throughout normal gestation, and does not perform the normal filtration of the infant liver. The liver does not perform digestive processes because the fetus does not consume meals directly, but receives nourishment from the mother via the placenta. The fetal liver releases some blood stem cells that migrate to the fetal thymus, so initially the lymphocytes, called T-cells, are created from fetal liver stem cells. Once the fetus is delivered, the formation of blood stem cells in infants shifts to the red bone marrow.

After birth, the umbilical vein and ductus venosus are completely obliterated in two to five days; the former becomes the ligamentum teres and the latter becomes the ligamentum venosum. In the disease state of cirrhosis and portal hypertension, the umbilical vein can open up again.

[edit] As food

Main article: Liver (food)

[edit] Cultural allusions

“	The liver has always been an important symbol in occult physiology. As the largest organ, the one containing the most blood, it was regarded as the darkest, least penetrable part of man's innards. Thus it was considered to contain the secret of fate and was used for fortune-telling. In Plato, and in later physiology, the liver represented the darkest passions, particularly the bloody, smoky ones of wrath, jealousy, and greed which drive men to action. Thus the liver meant the impulsive attachment to life itself.	”
—James Hillman[17]

In Greek mythology, Prometheus was punished by the gods for revealing fire to humans, by being chained to a rock where a vulture (or an eagle) would peck out his liver, which would regenerate overnight. (The liver is the only human internal organ that actually can regenerate itself to a significant extent.)

Many ancient peoples of the Near East and Mediterranean areas practised a type of divination called haruspicy, whereby they tried to obtain information from examining the livers of sheep and other animals.

The Talmud (tractate Berakhot 61b) refers to the liver as the seat of anger, with the gallbladder counteracting this.

The Persian, Urdu, and Hindi languages (جگر or जिगर or jigar) refer to the liver in figurative speech to indicate courage and strong feelings, or "their best"; e.g., "This Mecca has thrown to you the pieces of its liver!".^[18] The term jan e jigar, literally "the strength (power) of my liver", is a term of endearment in Urdu. In Persian slang, jigar is used as an adjective for any object which is desirable, especially women. In the Zulu language, the word for liver (isibindi) is the same as the word for courage.

The legend of Liver-Eating Johnson says that he would cut out and eat the liver of each man killed after dinner.

In the motion picture The Message, Hind bint Utbah is implied or portrayed eating the liver of Hamza ibn ‘Abd al-Muttalib during the Battle of Uhud. Although there are narrations that suggest that Hind did "taste", rather than eat, the liver of Hamza, the authenticity of these narrations have to be questioned.

[edit] See also

Look up liver in Wiktionary, the free dictionary.

• Artificial liver
• Bile
• Bile canaliculus
• Hepatocyte
• Liver function tests
• Liver shot (martial arts strike)
• Porto-Systemic anastomosis

[edit] References

This article includes a list of references, related reading or external links, but its sources remain unclear because it lacks inline citations. Please improve this article by introducing more precise citations where appropriate. (June 2008)

1. ^ Physiology at MCG 6/6ch2/s6ch2_30
2. ^ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337.
3. ^ The Greek word "ἡπαρ" was derived from hēpaomai (ηπάομαι): to mend, to repair, hence hēpar actually means "repairable", indicating that this organ can regenerate itself spontaneously in the case of lesion.
4. ^ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease. St. Louis, MO: Elsevier Saunders. pp. 878. ISBN 0-7216-0187-1.
5. ^ Benjamin L. Shneider; Sherman, Philip M. (2008). Pediatric Gastrointestinal Disease. Connecticut: PMPH-USA. pp. 751. ISBN 1-55009-364-9.
6. ^ "Three-dimensional Anatomy of the Couinaud Liver Segments". http://dpi.radiology.uiowa.edu/nlm/app/livertoc/liver/liver.html. Retrieved 2009-02-17.
7. ^ "Prof. Dr. Holger Strunk - Homepage". http://www.uni-bonn.de/~umm705/quiz0403.htm. Retrieved 2009-02-17.
8. ^ ^{a b} Romer, Alfred Sherwood; Parsons, Thomas S. (1977). The Vertebrate Body. Philadelphia, PA: Holt-Saunders International. pp. 354–355. ISBN 0-03-910284-X.
9. ^ Cirrhosis Overview National Digestive Diseases Information Clearinghouse. Retrieved on 2010-01-22
10. ^ Liver Tissue Damage And Treatment Retrieved on 2010-01-22
11. ^ Extraintestinal Complications: Liver Disease Crohn's & Colitis Foundation of America. Retrieved on 2010-01-22
12. ^ Liver Information HealthLine. Retrieved on 2010-01-22
13. ^ Liver.. The largest gland in the body MedicineNet. Retrieved on 2010-01-22
14. ^ Suzuki K, Tanaka M, Watanabe N, Saito S, Nonaka H, Miyajima A (July 2008). "p75 Neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver". Gastroenterology 135 (1): 270–281.e3. doi:10.1053/j.gastro.2008.03.075. PMID 18515089. http://linkinghub.elsevier.com/retrieve/pii/S0016-5085(08)00571-4.
15. ^ Michalopoulos, George K., and DeFrances, Marie C., "Liver regeneration:, Science, 4 April 1997: Vol. 276. no. 5309, pp. 60 - 66: "The ancient Greeks recognized liver regeneration in the myth of Prometheus. Having stolen the secret of fire from the gods of Olympus, Prometheus was condemned to having a portion of his liver eaten daily by an eagle. His liver regenerated overnight,"
16. ^ Bramstedt K (2006). "Living liver donor mortality: where do we stand?". Am. J. Gastrointestinal 101 (4): 755–9. doi:10.1111/j.1572-0241.2006.00421.x. PMID 16494593.
17. ^ Krishna, Gopi; Hillman, James (commentary) (1970). Kundalini – the evolutionary energy in man. London: Stuart & Watkins. pp. 77. SBN 7224 0115 9. http://www.scribd.com/doc/7577310/KUNDALINI-the-evolutionary-energy-in-man.
18. ^ THE GREAT BATTLE OF BADAR (Yaum-e-Furqan)

[edit] Further reading

The following are standard medical textbooks:

• Eugene R. Schiff, Michael F. Sorrell, Willis C. Maddrey, eds. Schiff's diseases of the liver, 9th ed. Philadelphia : Lippincott, Williams & Wilkins, 2003. ISBN 0-7817-3007-4
• Sheila Sherlock, James Dooley. Diseases of the liver and biliary system, 11th ed. Oxford, UK ; Malden, MA : Blackwell Science. 2002. ISBN 0-632-05582-0
• David Zakim, Thomas D. Boyer. eds. Hepatology: a textbook of liver disease, 4th ed. Philadelphia: Saunders. 2003. ISBN 0-7216-9051-3

These are for the lay reader or patient:

• Sanjiv Chopra. The Liver Book: A Comprehensive Guide to Diagnosis, Treatment, and Recovery, Atria, 2002, ISBN 0-7434-0585-4
• Melissa Palmer. Dr. Melissa Palmer's Guide to Hepatitis and Liver Disease: What You Need to Know, Avery Publishing Group; Revised edition May 24, 2004, ISBN 1-58333-188-3. her webpage.
• Howard J. Worman. The Liver Disorders Sourcebook, McGraw-Hill, 1999, ISBN 0-7373-0090-6. his Columbia University web site, "Diseases of the liver"

[edit] External links

Wikimedia Commons has media related to: Livers

• Liver at the Open Directory Project.
• VIRTUAL Liver - online learning resource

[show] v • d • e Human systems and organs TA 2-4: musculoskeletal Skeletal system Bone (Carpus · Collar bone (clavicle) · Thigh bone (femur) · Fibula · Humerus · Mandible · Metacarpus · Metatarsus · Ossicles · Patella · Phalanges · Radius · Skull (cranium) · Tarsus · Tibia · Ulna · Rib · Vertebra · Pelvis · Sternum) · Cartilage Joints Fibrous joint · Cartilaginous joint · Synovial joint Muscular system Muscle · Tendon · Diaphragm TA 5-11: splanchnic/ viscus mostly Thoracic Respiratory system URT (Nose, Nasopharynx, Larynx) · LRT (Trachea, Bronchus, Lung) mostly Abdominopelvic Digestive system+ adnexa Mouth (Salivary gland, Tongue) · upper GI (Oropharynx, Laryngopharynx, Esophagus, Stomach) · lower GI (Small intestine, Appendix, Colon, Rectum, Anus) · accessory (Liver, Biliary tract, Pancreas) GU: Urinary system Kidney · Ureter · Bladder · Urethra GU: Reproductive system Female (Uterus, Vulva, Ovary, Placenta) · Male (Scrotum, Penis, Prostate, Testicle, Seminal vesicle) Endocrine system Pituitary · Pineal · Thyroid · Parathyroid · Adrenal · Islets of Langerhans TA 12-16 Circulatory system Cardiovascular system peripheral (Artery, Vein) · Heart Lymphatic system primary (Bone marrow, Thymus) · secondary (Spleen, Lymph node) N/S Nervous system (Brain, Spinal cord, Nerve) · Sensory system (Ear, Eye) Integumentary system Skin · Subcutaneous tissue · Breast (Mammary gland) Non-TA Immune system general anatomy: systems and organs, regional anatomy, planes and lines, superficial axial anatomy, superficial anatomy of limbs

[show] v • d • e Anatomy of torso, digestive system: accessory digestive glands (TA A05.8-9, GA 11.1188) Liver by region: Left lobe • Right lobe (Caudate lobe, Quadrate lobe) • Transverse fissure of liver • Bare area of the liver by function: Fibrous capsule of Glisson • Hepatocyte • Space of Disse • Space of Mall • Kupffer cell • Liver sinusoid • Hepatic stellate cell • Hepatic lobule Biliary tract Bile ducts intrahepatic: Bile canaliculus • Canals of Hering • Interlobular bile ducts • Intrahepatic bile ducts • Left and Right hepatic ducts extrahepatic: Common hepatic duct • Cystic duct • Common bile duct Gallbladder by region: Body • Fundus • Neck Pancreas by region: Tail • Body • Neck • Head • Uncinate process by function: Islets of Langerhans • Exocrine pancreas ducts: Pancreatic duct • Accessory pancreatic duct Common Hepatopancreatic ampulla • Sphincter of Oddi M: DIG anat(t,g,p)/phys/devp/cell noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16)

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