Cirrhosis

From Wikipedia, the free encyclopedia - View original article

Cirrhosis
Classification and external resources
Hepaticfailure.jpg
The abdomen of a person with cirrhosis showing massive ascites and caput medusae
ICD-10K70.3, K71.7, K74
ICD-9571
DiseasesDB2729
MedlinePlus000255
eMedicinemed/3183 radio/175
Patient UKCirrhosis
MeSHD008103
 
Jump to: navigation, search
Cirrhosis
Classification and external resources
Hepaticfailure.jpg
The abdomen of a person with cirrhosis showing massive ascites and caput medusae
ICD-10K70.3, K71.7, K74
ICD-9571
DiseasesDB2729
MedlinePlus000255
eMedicinemed/3183 radio/175
Patient UKCirrhosis
MeSHD008103

Cirrhosis /sɪˈrsɪs/ (from Greek kirrhos [κιρρός] "yellowish" and the common Greek suffix -sis meaning "condition") is a result of advanced liver disease. It is characterized by replacement of liver tissue by fibrosis (scar tissue) and regenerative nodules (lumps that occur due to attempted repair of damaged tissue).[1][2][3] These changes lead to loss of liver function. Cirrhosis is most commonly caused by alcoholism, hepatitis B and hepatitis C, and fatty liver disease, but has many other possible causes. Some cases are idiopathic (of unknown cause).

Ascites (fluid retention in the abdominal cavity) is the most common complication of cirrhosis. It is associated with a poor quality of life, increased risk of infection, and a poor long-term outcome. Other potentially life-threatening complications are hepatic encephalopathy (confusion and coma) and bleeding from esophageal varices. Cirrhosis is irreversible, and treatment usually focuses on preventing progression and complications. In advanced stages of cirrhosis the only option is a liver transplant.

Signs and symptoms[edit]

Cirrhosis has many possible manifestations. These signs and symptoms may be either as a direct result of the failure of liver cells or secondary to the resultant portal hypertension. There are also some manifestations whose causes are nonspecific but may occur in cirrhosis. Likewise, the absence of any does not rule out the possibility of cirrhosis.[4]

Liver dysfunction[edit]

The following features are as a direct consequence of liver cells not functioning.

Portal hypertension[edit]

Liver cirrhosis increases resistance to blood flow and higher pressure in the portal venous system, resulting in portal hypertension. Effects of portal hypertension include:

Unestablished cause[edit]

There are some changes seen in cirrhosis whose causes are not clearly known. They may also be a sign of other non-liver related causes.

Advanced disease[edit]

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

Causes[edit]

It has many possible causes; sometimes more than one cause is present in the same person. Globally, 57% of cirrhosis is attributable to either hepatitis B (30%) or hepatitis C (27%).[15] Alcohol consumption is another important cause, accounting for about 20% of the cases.[15]

Pathophysiology[edit]

The liver plays a vital role in synthesis of proteins (for example, albumin, clotting factors and complement), detoxification, and storage (for example, vitamin A). In addition, it participates in the metabolism of lipids and carbohydrates.

Cirrhosis is often preceded by hepatitis and fatty liver (steatosis), independent of the cause. If the cause is removed at this stage, the changes are still fully reversible.

The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal parenchyma. This scar tissue blocks the portal flow of blood through the organ therefore disturbing normal function. Recent research shows the pivotal role of the stellate cell, a cell type that normally stores vitamin A, in the development of cirrhosis. Damage to the hepatic parenchyma (due to inflammation) leads to activation of the stellate cell, which increases fibrosis (called myofibroblast) and obstructs blood flow in the circulation.[20] In addition, it secretes TGF-β1, which leads to a fibrotic response and proliferation of connective tissue. Furthermore, it secretes TIMP 1 and 2, naturally occurring inhibitors of matrix metalloproteinases, which prevents them from breaking down fibrotic material in the extracellular matrix.[21][22]

The fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, which leads to hypersplenism and increased sequestration of platelets. Portal hypertension is responsible for most severe complications of cirrhosis.

Diagnosis[edit]

Micrograph showing cirrhosis. Trichrome stain.

The gold standard for diagnosis of cirrhosis is a liver biopsy, through a percutaneous, transjugular, laparoscopic, or fine-needle approach. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggests cirrhosis. Furthermore, there is a small but significant risk to liver biopsy, and cirrhosis itself predisposes for complications caused by liver biopsy.[23] The best predictors of cirrhosis are ascites, platelet count <160,000/mm3, spider angiomata and Bonacini cirrhosis discriminant score greater than 7.[24]

Lab findings[edit]

The following findings are typical in cirrhosis:

There is now a validated and patented combination of 6 of these markers as non-invasive biomarker of fibrosis (and so of cirrhosis): FibroTest.[26]

Other laboratory studies performed in newly diagnosed cirrhosis may include:

Imaging[edit]

Liver cirrhosis as seen on an axial CT of the abdomen.

Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and nodular liver in advanced cirrhosis along with increased echogenicity with irregular appearing areas. Other findings suggestive of cirrhosis in imaging are an enlarged caudate lobe, widening of the liver fissures and enlargement of the spleen. An enlarged spleen (splenomegaly), which normally measures less than 11–12 cm in adults, is suggestive of cirrhosis with portal hypertension in the right clinical setting. Ultrasound may also screen for hepatocellular carcinoma, portal hypertension, and Budd-Chiari syndrome (by assessing flow in the hepatic vein).

Cirrhosis is diagnosed with a variety of elastography techniques. Because a cirrhotic liver is generally stiffer than a healthy one, imaging the liver's stiffness can give diagnostic information about the location and severity of cirrhosis. Techniques used include transient elastography, acoustic radiation force impulse imaging, supersonic shear imaging and magnetic resonance elastography. Compared to a biopsy, elastography can sample a much larger area and is painless. It shows reasonable correlation with the severity of cirrhosis.[27]

Other tests performed in particular circumstances include abdominal CT and liver/bile duct MRI (MRCP).

Endoscopy[edit]

Gastroscopy (endoscopic examination of the esophagus, stomach, and duodenum) is performed in patients with established cirrhosis to exclude the possibility of esophageal varices. If these are found, prophylactic local therapy may be applied (sclerotherapy or banding) and beta blocker treatment may be commenced.

Rarely are diseases of the bile ducts, such as primary sclerosing cholangitis, causes of cirrhosis. Imaging of the bile ducts, such as ERCP or MRCP (MRI of biliary tract and pancreas) may aid in the diagnosis.

Pathology[edit]

Cirrhosis leading to hepatocellular carcinoma (autopsy specimen).

Macroscopically, the liver is initially enlarged, but with progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and the color is often yellow (if associated steatosis). Depending on the size of the nodules there are three macroscopic types: micronodular, macronodular, and mixed cirrhosis. In micronodular form (Laennec's cirrhosis or portal cirrhosis) regenerating nodules are under 3 mm. In macronodular cirrhosis (post-necrotic cirrhosis), the nodules are larger than 3 mm. The mixed cirrhosis consists of nodules with different sizes.

However, cirrhosis is defined by its pathological features on microscopy: (1) the presence of regenerating nodules of hepatocytes and (2) the presence of fibrosis, or the deposition of connective tissue between these nodules. The pattern of fibrosis seen can depend upon the underlying insult that led to cirrhosis. Fibrosis can also proliferate even if the underlying process that caused it has resolved or ceased. The fibrosis in cirrhosis can lead to destruction of other normal tissues in the liver: including the sinusoids, the space of Disse, and other vascular structures, which leads to altered resistance to blood flow in the liver and portal hypertension.[28]

As cirrhosis can be caused by many different entities which injure the liver in different ways, cause specific abnormalities may be seen. For example, in chronic hepatitis B, there is infiltration of the liver parenchyma with lymphocytes.[28] In cardiac cirrhosis there are erythrocytes and a greater amount of fibrosis in the tissue surrounding the hepatic veins.[29] In primary biliary cirrhosis, there is fibrosis around the bile duct, the presence of granulomas and pooling of bile.[30] Lastly in alcoholic cirrhosis, there is infiltration of the liver with neutrophils.[28]

Grading[edit]

The severity of cirrhosis is commonly classified with the Child-Pugh score. This score uses bilirubin, albumin, INR, presence and severity of ascites, and encephalopathy to classify patients in class A, B, or C. Class A has a favourable prognosis, while class C is at high risk of death. It was devised in 1964 by Child and Turcotte and modified in 1973 by Pugh and others.[31]

More modern scores, used in the allocation of liver transplants but also in other contexts, are the Model for End-Stage Liver Disease (MELD) score and its pediatric counterpart, the Pediatric End-Stage Liver Disease (PELD) score.

The hepatic venous pressure gradient, (difference in venous pressure between afferent and efferent blood to the liver) also determines severity of cirrhosis, although hard to measure. A value of 16 mm or more means a greatly increased risk of dying.[32]

Prevention[edit]

Key prevention strategies for cirrhosis and its compensation are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.[citation needed]

Little is known on modulators of cirrhosis risk and progression. Coffee consumption appears to help protect against cirrhosis.[33][34]

Management[edit]

Generally, liver damage from cirrhosis cannot be reversed, but treatment could stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease risk of constipation; their role in preventing encephalopathy is limited.

Alcoholic cirrhosis caused by alcohol abuse is treated by abstaining from alcohol. Treatment for hepatitis-related cirrhosis involves medications used to treat the different types of hepatitis, such as interferon for viral hepatitis and corticosteroids for autoimmune hepatitis. Cirrhosis caused by Wilson's disease, in which copper builds up in organs, is treated with chelation therapy (for example, penicillamine) to remove the copper.

Preventing further liver damage[edit]

Regardless of underlying cause of cirrhosis, alcohol and paracetamol, as well as other potentially damaging substances, are discouraged. Vaccination of susceptible patients should be considered for Hepatitis A and Hepatitis B.

Transplantation[edit]

Main article: Liver transplantation

If complications cannot be controlled or when the liver ceases functioning, liver transplantation is necessary. Survival from liver transplantation has been improving over the 1990s, and the five-year survival rate is now around 80%. The survival rate depends largely on the severity of disease and other medical problems in the recipient.[35] In the United States, the MELD score is used to prioritize patients for transplantation.[36] Transplantation necessitates the use of immune suppressants (cyclosporine or tacrolimus).

Decompensated cirrhosis[edit]

In patients with previously stable cirrhosis, decompensation may occur due to various causes, such as constipation, infection (of any source), increased alcohol intake, medication, bleeding from esophageal varices or dehydration. It may take the form of any of the complications of cirrhosis listed below.

Patients with decompensated cirrhosis generally require admission to hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment - often with diuretics, antibiotics, laxatives and/or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline. Administration of saline is avoided as it would add to the already high total body sodium content that typically occurs in cirrhosis.

Palliative care[edit]

Palliative care is specialized medical care that focuses on providing patients with relief from the symptoms, pain, and stress of a serious illness, such as cirrhosis. The goal of palliative care is to improve quality of life for both the patient and the patient's family and it is appropriate at any stage and for any type of cirrhosis.[37]

Especially in the later stages, people with cirrhosis experience significant symptoms such as abdominal swelling, itching, leg edema, and chronic abdominal pain which would be amenable for treatment through palliative care.[38] Because the disease is not curable without a transplant, palliative care can also help with discussions regarding the person's wishes concerning health care power of attorney, Do Not Resuscitate decisions and life support, and potentially hospice.[38] People with cirrhosis are rarely referred to palliative care.[39]

Complications[edit]

Ascites[edit]

Salt restriction is often necessary, as cirrhosis leads to accumulation of salt (sodium retention). Diuretics may be necessary to suppress ascites. Diuretic options for inpatient treatment include aldosterone antagonists (spironolactone) and loop diuretics. Aldosterone antagonists are preferred for people who can take oral medications and are not in need of an urgent volume reduction. Loop diuretics can be added as additional therapy.[40]

If a rapid reduction of volume is required, paracentesis is the preferred option. This procedure requires the insertion of a plastic tube into the peritoneal cavity. Human albumin solution is usually given to prevent complications from the rapid reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy.[40]

Esophageal variceal bleeding[edit]

For portal hypertension, propranolol is a commonly used agent to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting is occasionally indicated to relieve pressure on the portal vein. As this shunting can worsen encephalopathy, it is reserved for those patients at low risk of encephalopathy. TIPS is generally regarded only as a bridge to liver transplantation or as a palliative measure.

Hepatic encephalopathy[edit]

High-protein food increases the nitrogen balance, and would theoretically increase encephalopathy; in the past, this was therefore eliminated as much as possible from the diet. Recent studies show that this assumption was incorrect, and high-protein foods are even encouraged to maintain adequate nutrition.[41]

Hepatorenal syndrome[edit]

The hepatorenal syndrome is defined as a urine sodium less than 10 mmol/L and a serum creatinine > 1.5 mg/dl (or 24 hour creatinine clearance less than 40 ml/min) after a trial of volume expansion without diuretics.[42]

Spontaneous bacterial peritonitis[edit]

People with ascites due to cirrhosis are at risk of spontaneous bacterial peritonitis.

Portal hypertensive gastropathy[edit]

Which refers to changes in the mucosa of the stomach in people with portal hypertension, and is associated with cirrhosis severity.[43]

Infection[edit]

Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be aspecific and are more difficult to recognize (for example, worsening encephalopathy but no fever).

Hepatocellular carcinoma[edit]

Hepatocellular carcinoma is a primary liver cancer that is more common in people with cirrhosis. People with known cirrhosis are often screened intermittently for early signs of this tumor, and screening has been shown to improve outcomes.[44]

Epidemiology[edit]

Disability-adjusted life year for cirrhosis of the liver per 100,000 inhabitants in 2004.[45]
  no data
  <50
  50-100
  100-200
  200-300
  300-400
  400-500
  500-600
  600-700
  700-800
  800-900
  900-1000
  >1000

Cirrhosis and chronic liver disease were the tenth leading cause of death for men and the twelfth for women in the United States in 2001, killing about 27,000 people each year.[46] Also, the cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.

Established cirrhosis has a 10-year mortality of 34–66%, largely dependent on the cause of the cirrhosis; alcoholic cirrhosis has a worse prognosis than primary biliary cirrhosis and cirrhosis due to hepatitis. The risk of death due to all causes is increased twelvefold; if one excludes the direct consequences of the liver disease, there is still a fivefold increased risk of death in all disease categories.[47]

Etymology[edit]

The word "cirrhosis" derives from Greek κιρρός [kirrhós] meaning yellowish, tawny (the orange-yellow colour of the diseased liver) + the common Greek suffix of the third declension -sis known from other Greek-originated terms (such as ly-sis, amyloido-sis, necro-sis etc.) that in Greek means "condition" (thus cirrho+sis = a yellowish condition or a condition that makes one yellowish). While the clinical entity was known before, it was René Laennec who gave it the name "cirrhosis" (in the same 1819 work in which he also described the stethoscope).[48]

References[edit]

  1. ^ "Cirrhosis – MayoClinic.com". 
  2. ^ "Liver Cirrhosis". Review of Pathology of the Liver. 
  3. ^ "Pathology Education: Gastrointestinal". 
  4. ^ a b c d e f g h Friedman LS (2014). Current medical diagnosis and treatment 2014. [S.l.]: Mcgraw-Hill. pp. Chapter 16. Liver, Biliary Tract, & Pancreas Disorders. ISBN 978-0071806336. 
  5. ^ Li CP, Lee FY, Hwang SJ, et al. (1999). "Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function". Scand. J. Gastroenterol. 34 (5): 520–3. doi:10.1080/003655299750026272. PMID 10423070. 
  6. ^ william, james (2005). Andrews' Diseases of the Skin: Clinical Dermatology. saunders. ISBN 0-7216-2921-0. 
  7. ^ Slater, Joseph S. Esherick, Daniel S. Clark, Evan D. Current practice guidelines in primary care 2013. New York: McGraw-Hill Medical. pp. Chapter 3: Disease Management. ISBN 0071797505. 
  8. ^ Van Thiel, DH; Gavaler, JS; Schade, RR (February 1985). "Liver disease and the hypothalamic pituitary gonadal axis.". Seminars in liver disease 5 (1): 35–45. doi:10.1055/s-2008-1041756. PMID 3983651. 
  9. ^ van Thiel, DH; Gavaler, JS; Spero, JA; Egler, KM; Wright, C; Sanghvi, AT; Hasiba, U; Lewis, JH (Jan–Feb 1981). "Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies.". Hepatology (Baltimore, Md.) 1 (1): 39–46. doi:10.1002/hep.1840010107. PMID 6793494. 
  10. ^ a b c d e f g h i j k l m n o p q al.], ed. Dan L. Longo ... [et (2012). Harrison's principles of internal medicine. (18th ed. ed.). New York: McGraw-Hill. pp. Chapter 308. Cirrhosis and Its Complications. ISBN 9780071748896. 
  11. ^ Tangerman, A; Meuwese-Arends, MT; Jansen, JB (Feb 19, 1994). "Cause and composition of foetor hepaticus.". Lancet 343 (8895): 483. doi:10.1016/s0140-6736(94)92729-4. PMID 7905979. 
  12. ^ Suurmond, D. (2009). Color Atlas and Synopsis of Clinical Dermatology: Common and Serious Diseases. McGraw-Hill. pp. Section 33: Disorders of the nail apparatus. ISBN 978-0071793025. 
  13. ^ a b c d Suurmond, D. (2009). Fitzpatrick's Color Atlas & Synopsis of Clinical Dermatology. 6th ed. New York: McGraw-Hill. pp. Section 33. Disorders of the Nail Apparatus. 
  14. ^ Longo et al. Harrison's Principles of Internal Medicine, 18th ed., p.2295
  15. ^ a b Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP (October 2006). "The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide". J. Hepatol. 45 (4): 529–38. doi:10.1016/j.jhep.2006.05.013. PMID 16879891. 
  16. ^ Alcohol-Induced Liver Disease; http://www.liverfoundation.org/abouttheliver/info/alcohol/
  17. ^ al.], ed. Dan L. Longo ... [et (2011). Harrison's principles of internal medicine. (18th ed. ed.). New York: McGraw-Hill. p. Liver Transplantation. ISBN 9780071748896. 
  18. ^ Edwards, CQ; Kushner, JP (Jun 3, 1993). "Screening for hemochromatosis.". The New England Journal of Medicine 328 (22): 1616–20. doi:10.1056/NEJM199306033282208. PMID 8110209. 
  19. ^ Tanner, MS (May 1998). "Role of copper in Indian childhood cirrhosis.". The American journal of clinical nutrition 67 (5 Suppl): 1074S–1081S. PMID 9587155. 
  20. ^ Hammer, edited by Stephen J. McPhee, Gary D. (2010). Pathophysiology of disease : an introduction to clinical medicine (6th ed. ed.). New York: McGraw-Hill Medical. pp. Chapter 14: Liver Disease. Cirrhosis. ISBN 978-0071621670. 
  21. ^ Iredale JP (2003). "Cirrhosis: new research provides a basis for rational and targeted treatments". BMJ 327 (7407): 143–7. doi:10.1136/bmj.327.7407.143. PMC 1126509. PMID 12869458. 
  22. ^ Puche, JE; Saiman, Y; Friedman, SL (Oct 1, 2013). "Hepatic stellate cells and liver fibrosis.". Comprehensive Physiology 3 (4): 1473–92. doi:10.1002/cphy.c120035. PMID 24265236. 
  23. ^ Grant, A; Neuberger J (1999). "Guidelines on the use of liver biopsy in clinical practice". Gut 45 (Suppl 4): 1–11. doi:10.1136/gut.45.2008.iv1. PMC 1766696. PMID 10485854. The main cause of mortality after percutaneous liver biopsy is intraperitoneal haemorrhage as shown in a retrospective Italian study of 68 000 percutaneous liver biopsies in which all six patients who died did so from intraperitoneal haemorrhage. Three of these patients had had a laparotomy, and all had either cirrhosis or malignant disease, both of which are risk factors for bleeding. 
  24. ^ Udell, JA; Wang, CS, Tinmouth, J, FitzGerald, JM, Ayas, NT, Simel, DL, Schulzer, M, Mak, E, Yoshida, EM (Feb 22, 2012). "Does this patient with liver disease have cirrhosis?". JAMA: the Journal of the American Medical Association 307 (8): 832–42. doi:10.1001/jama.2012.186. PMID 22357834. 
  25. ^ a b Maddrey, edited by Eugene R. Schiff, Michael F. Sorrell & Willis C. (1999). Schiff's diseases of the liver. (11th ed. / edited by Eugene R. Schiff, Willis C. Maddrey, Michael F. Sorrell. ed.). Chichester, West Sussex, UK: John Wiley & Sons. pp. Evaluation of the Liver A: Laboratory Test. ISBN 978-0-470-65468-2. 
  26. ^ Halfon P, Munteanu M, Poynard T (2008). "FibroTest-ActiTest as a non-invasive marker of liver fibrosis". Gastroenterol Clin Biol 32 (6): 22–39. doi:10.1016/S0399-8320(08)73991-5. PMID 18973844. 
  27. ^ Foucher J, Chanteloup E, Vergniol J, et al. (2006). "Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study". Gut 55 (3): 403–8. doi:10.1136/gut.2005.069153. PMC 1856085. PMID 16020491. 
  28. ^ a b c Brenner, David; Richard A. Rippe (2003). "Pathogenesis of Hepatic Fibrosis". In Tadataka Yamada. Textbook of Gastroenterology 2 (4th ed.). Lippincott Williams & Wilkins. ISBN 978-0-7817-2861-4. 
  29. ^ Giallourakis CC, Rosenberg PM, Friedman LS (November 2002). "The liver in heart failure". Clin Liver Dis 6 (4): 947–67, viii–ix. doi:10.1016/S1089-3261(02)00056-9. PMID 12516201. 
  30. ^ Heathcote EJ (November 2003). "Primary biliary cirrhosis: historical perspective". Clin Liver Dis 7 (4): 735–40. doi:10.1016/S1089-3261(03)00098-9. PMID 14594128. 
  31. ^ Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973). "Transection of the oesophagus for bleeding oesophageal varices". Br J Surg 60 (8): 646–9. doi:10.1002/bjs.1800600817. PMID 4541913. 
  32. ^ Patch D, Armonis A, Sabin C, et al. (1999). "Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding". Gut 44 (2): 264–9. doi:10.1136/gut.44.2.264. PMC 1727391. PMID 9895388. 
  33. ^ Muriel, P; Arauz, J (Jul 2010). "Coffee and liver diseases.". Fitoterapia 81 (5): 297–305. doi:10.1016/j.fitote.2009.10.003. PMID 19825397. 
  34. ^ Masterton GS, Hayes PC (November 2010). "Coffee and the liver: a potential treatment for liver disease?". Eur J Gastroenterol Hepatol 22 (11): 1277–83. doi:10.1097/MEG.0b013e32833cca96. PMID 20802342. 
  35. ^ "E-medicine liver transplant outlook and survival rates". Emedicinehealth.com. 2009-06-09. Retrieved 2009-09-06. 
  36. ^ Kamath PS, Kim WR (March 2007). "The model for end-stage liver disease (MELD)". Hepatology 45 (3): 797–805. doi:10.1002/hep.21563. PMID 17326206. 
  37. ^ Ferrell, B; Connor, SR; Cordes, A; Dahlin, CM; Fine, PG; Hutton, N; Leenay, M; Lentz, J; Person, JL; Meier, DE; Zuroski, K; National Consensus Project for Quality Palliative Care Task Force, Members (Jun 2007). "The national agenda for quality palliative care: the National Consensus Project and the National Quality Forum.". Journal of pain and symptom management 33 (6): 737–44. doi:10.1016/j.jpainsymman.2007.02.024. PMID 17531914. 
  38. ^ a b Sanchez, W; Talwalkar, JA (Mar 2006). "Palliative care for patients with end-stage liver disease ineligible for liver transplantation.". Gastroenterology clinics of North America 35 (1): 201–19. doi:10.1016/j.gtc.2005.12.007. PMID 16530121. 
  39. ^ Poonja, Z; Brisebois, A; van Zanten, SV; Tandon, P; Meeberg, G; Karvellas, CJ (Apr 2014). "Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management.". Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 12 (4): 692–8. doi:10.1016/j.cgh.2013.08.027. PMID 23978345. 
  40. ^ a b Moore KP, Aithal GP (October 2006). "Guidelines on the management of ascites in cirrhosis". Gut. 55 Suppl 6 (Suppl 6): vi1–12. doi:10.1136/gut.2006.099580. PMC 1860002. PMID 16966752. 
  41. ^ Sundaram V, Shaikh OS (July 2009). "Hepatic encephalopathy: pathophysiology and emerging therapies". Med. Clin. North Am. 93 (4): 819–36, vii. doi:10.1016/j.mcna.2009.03.009. PMID 19577116. 
  42. ^ Ginés P, Arroyo V, Quintero E, et al. (1987). "Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study". Gastroenterology 93 (2): 234–41. PMID 3297907. 
  43. ^ Kim MY, Choi H, Baik SK, et al. (April 2010). "Portal Hypertensive Gastropathy: Correlation with Portal Hypertension and Prognosis in Cirrhosis". Dig Dis Sci 55 (12): 3561–7. doi:10.1007/s10620-010-1221-6. PMID 20407828. 
  44. ^ Singal AG, Pillai A, Tiro J (2014). "Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis". PLoS Med 11 (4): e1001624. doi:10.1371/journal.pmed.1001624. PMC 3972088. PMID 24691105. 
  45. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. Retrieved Nov 11, 2009. 
  46. ^ Anderson RN, Smith BL (2003). "Deaths: leading causes for 2001". National Vital Statistics Reports (Centers for Disease Control and Prevention) 52 (9): 1–85. PMID 14626726. 
  47. ^ Sørensen HT, Thulstrup AM, Mellemkjar L, et al. (2003). "Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark". Journal of Clinical Epidemiology 56 (1): 88–93. doi:10.1016/S0895-4356(02)00531-0. PMID 12589875. 
  48. ^ Roguin A (2006). "Rene Theophile Hyacinthe Laënnec (1781–1826): The Man Behind the Stethoscope". Clinical medicine & research 4 (3): 230–5. doi:10.3121/cmr.4.3.230. PMC 1570491. PMID 17048358. 

External links[edit]