• Clinical science

Cirrhosis

Summary

Cirrhosis is a condition caused by chronic damage to the liver, most commonly due to excessive alcohol consumption or hepatitis C infection. Other causes may include inflammatory or metabolic diseases, such as primary biliary cirrhosis or hemochromatosis. Cirrhosis is characterized by hepatic parenchymal necrosis and an inflammatory response to the underlying cause. Subsequent hepatic repair mechanisms lead to fibrosis and abnormal tissue architecture, which impair liver function. Patients may present with a range of symptoms, including jaundice, ascites, hepatosplenomegaly, and typical skin manifestations such as spider angioma or palmar erythema. Men may further display signs of feminization (e.g., gynecomastia, hypogonadism). In severe cases, accumulation of toxic metabolites or involvement of further organs can lead to complications such as hepatic encephalopathy or hepatorenal syndrome. Laboratory tests show signs of hepatocyte destruction (e.g., elevated liver enzymes, hyperbilirubinemia) or impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal ultrasonography typically shows a shrunken, heterogeneous liver parenchyma with a nodular surface. Biopsy is the method of choice for confirming the diagnosis. However, it is usually only performed if previous testing was inconclusive. Management consists of treatment of the underlying disease (e.g., avoiding toxic substances, antiviral drugs), adequate calorie intake, and medication for treating complications (e.g., spironolactone for ascites). In cases of decompensated cirrhosis, interventional procedures (e.g., paracentesis to drain ascites) may be used to alleviate symptoms or bridge the time until liver transplantation is possible.

Epidemiology

  • Prevalence: approx. 0.27% in U.S. adults
  • Sex: > (2:1)
  • Responsible for approx. 1–2% of all deaths in the United States; most deaths occurring in the fifth to sixth decade of life

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Alcoholic liver disease, Hepatitis C, and NASH are the most common causes of cirrhosis in the US.
References:[1][3][4][5][6][7]

Classification

Child-Pugh score
Points 1 2 3
Serum albumin g/dL > 3.5 2.8–3.5 < 2.8
Serum bilirubin mg/dL < 2.0 2.0–3.0 > 3.0
INR < 1.7 1.7–2.3 > 2.3
Ascites None Mild Moderate
Hepatic encephalopathy None Minimal Advanced
Child-Pugh class A: 5–6 points; Child-Pugh class B: 7–9 points; Child-Pugh class C: 10–15 points

References:[8][9]

Pathophysiology

References:[10]

Clinical features

Gynecomastia can also be caused by treatment with spironolactone!
References:[8][11][1][5][12]

Diagnostics

Laboratory tests

Imaging studies

  • Abdominal ultrasound should be performed first. Possible findings include:
    • Liver form and structure
      • Nodular liver surface
      • Atrophy of the right lobe
      • Loss of structural homogeneity (hyperechoic or variable increase in echogenicity) with fibrous septa.
    • Liver size: initially enlarged, atrophies and shrinks with disease progression
    • Other possible findings
  • CT scan
    • Typical findings

Biopsy

  • Indication: Although biopsy is the gold standard for diagnosis, it is unnecessary in the light of clinical, laboratory, and ultrasound evidence. However, it can aid in identifying the etiology of the cirrhosis if prior testing was inconclusive.

Screening procedures and monitoring the disease course

Before taking a biopsy, check the patient's coagulation status as the risk of bleeding may be increased!

References:[8][11][5][13][14][15]

Pathology

  • Findings
    • Fibrosis
    • Replacement of normal liver tissue with collagenous regenerative nodules (histological staging is based on the size of the regenerative nodules)
Size of the regenerative nodules Occurrence
Micronodular 1–3 mm
Macronodular > 3 mm
Both 1–3 mm and > 3 mm
  • Possible in every type of liver‑damaging disease

Treatment

References:[16][17][18][19]

Complications

The following complications are covered in separate sections below or in other separate cards:

Decompensated cirrhosis

The associated ascites and edema as well as the high risk of bleeding considerably increase the risk for hypovolemic shock!

References:[8][20]

We list the most important complications. The selection is not exhaustive.

Hepatic encephalopathy

Definition: Hepatic encephalopathy (HE) is defined as fluctuations in mental status and cognitive function in the presence of severe liver disease. Hepatic dysfunction results in inadequate elimination of metabolic products with subsequent accumulation of neurotoxic metabolites (like ammonia).

  • Treatment
    • General measures
      • Avoidance of trigger substances (e.g., hepatotoxic medication, alcohol)
      • Treatment of further complications which might aggravate HE (see “Triggers” above)
    • Lactulose: synthetic disaccharide laxative
      • First-line treatment for HE
      • Improves HE by decreasing absorption of ammonia in the bowel: lactulose is converted to lactic acid by intestinal floraacidification in the gut leads to conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentration
    • Rifaximin [21]
      • Non‑absorbable antibiotic
      • May be added to lactulose to prevent recurrent episodes of HE after the second episode

References:[20][22][17][23][24][25][26][27][21][28]

Hepatorenal syndrome (HRS)

References:[29][30]

Portal vein thrombosis

References:[31][32]

Pulmonary complications of portal hypertension

References:[33][34]

Prognosis

  • Survival is poor in patients with decompensated cirrhosis unless they receive liver transplantation.
  • One‑year survival rate based on Child‑Pugh score:
    • Child‑Pugh class A: almost normal
    • Child‑Pugh class B: 80%
    • Child‑Pugh class C: 45%

References:[9]

  • 1. Wolf DC. Cirrhosis. In: Anand BS. Cirrhosis. New York, NY: WebMD. http://emedicine.medscape.com/article/185856. Updated January 8, 2017. Accessed March 25, 2017.
  • 2. Scaglione S, Kliethermes S, Cao G, et al. The Epidemiology of Cirrhosis in the United States: A Population-based Study. J Clin Gastroenterol. 2015; 49(8): pp. 690–696. doi: 10.1097/MCG.0000000000000208.
  • 3. Tommolino E. Fatty Liver. In: Anand BS. Fatty Liver. New York, NY: WebMD. http://emedicine.medscape.com/article/175472. Updated January 25, 2017. Accessed March 25, 2017.
  • 4. Starr SP, Raines D. Cirrhosis: Diagnosis, Management, and Prevention. Am Fam Physician. 2011; 84(12): pp. 1353–1359. url: http://www.aafp.org/afp/2011/1215/p1353.html.
  • 5. Goldberg E, Chopra S. Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/cirrhosis-in-adults-etiologies-clinical-manifestations-and-diagnosis. Last updated August 15, 2016. Accessed March 29, 2017.
  • 6. Kuniholm MH, Lesi OA, Mendy M, et al. Aflatoxin exposure and viral hepatitis in the etiology of liver cirrhosis in the Gambia, West Africa. Environ Health Perspect. 2008; 116(11): pp. 1553–7. doi: 10.1289/ehp.11661.
  • 7. Garcia-Tsao G, Korzenik JR, Young L, et al. Liver Disease in Patients with Hereditary Hemorrhagic Telangiectasia. N Engl J Med. 2000; 343(13): pp. 931–936. doi: 10.1056/nejm200009283431305.
  • 8. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. New York, NY: McGraw-Hill Education; 2015.
  • 9. Friedman LS. Liver biochemical tests that detect injury to hepatocytes. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/liver-biochemical-tests-that-detect-injury-to-hepatocytes. Last updated March 9, 2017. Accessed March 29, 2017.
  • 10. Goljan EF. Rapid Review Pathology. Philadelphia, PA: Elsevier Saunders; 2018.
  • 11. Jenkins B, McInnis M, Lewis C. Step-Up to USMLE Step 2 CK. Lippincott Williams & Wilkins; 2015.
  • 12. Cavanaugh J, Niewoehner CB, Nuttall FQ. Gynecomastia and cirrhosis of the liver. Arch Intern Med. 1990; 150(3): pp. 563–565. pmid: 2310274.
  • 13. Meng F, Yin X, Ma X, Guo XD, Jin B, Li H. Assessment of the value of serum cholinesterase as a liver function test for cirrhotic patients. Biomed Rep. 2013; 1(2): pp. 265–268. doi: 10.3892/br.2013.60.
  • 14. Qamar AA, Grace ND. Abnormal hematological indices in cirrhosis. Can J Gastroenterol. 2009; 23(6): pp. 441–445. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721814/.
  • 15. Colombo M, Sirlin CB. Surveillance for Hepatocellular Carcinoma in Adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/surveillance-for-hepatocellular-carcinoma-in-adults. Last updated May 1, 2018. Accessed May 9, 2018.
  • 16. Koff RS. Immunizations for patients with chronic liver disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/immunizations-for-patients-with-chronic-liver-disease. Last updated May 28, 2015. Accessed March 29, 2017.
  • 17. Ferenci P. Hepatic encephalopathy in adults: Treatment. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-treatment. Last updated February 25, 2016. Accessed March 29, 2017.
  • 18. Carale J. Portal Hypertension. In: Portal Hypertension. New York, NY: WebMD. http://emedicine.medscape.com/article/182098. Updated November 20, 2016. Accessed March 29, 2017.
  • 19. Such J, Runyon BA. Ascites in adults with cirrhosis: Initial therapy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/ascites-in-adults-with-cirrhosis-initial-therapy. Last updated April 17, 2015. Accessed March 29, 2017.
  • 20. Agabegi SS, Agabegi ED. Step-Up To Medicine. Baltimore, MD, USA: Wolters Kluwer Health; 2015.
  • 21. Vilstrup H. Hepatic Encephalopathy in Chronic Liver Disease: 2014 Practice Guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases. J Hepatol. 2014; 61(3): pp. 642–659. doi: 10.1016/j.jhep.2014.05.042.
  • 22. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education; 2015.
  • 23. Sood GK. Portal-Systemic Encephalopathy. In: Portal-Systemic Encephalopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/182208. Updated December 18, 2014. Accessed March 29, 2017.
  • 24. Wolf DC. Hepatic Encephalopathy. In: Hepatic Encephalopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/186101-overview. Updated January 30, 2017. Accessed March 29, 2017.
  • 25. Torres DS, Abrantes J, Brandão-mello CE. Cognitive assessment of patients with minimal hepatic encephalopathy in Brazil. Metab Brain Dis. 2013; 28(3): pp. 473–483. doi: 10.1007/s11011-013-9405-3.
  • 26. Li SW, Wang K, Yu YQ, Wang HB, Li YH, Xu JM. Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China. World J Gastroenterol. 2013; 19(46): pp. 8745–8751. doi: 10.3748/wjg.v19.i46.8745.
  • 27. Shaker M, Carey WD. Hepatic Encephalopathy. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatic-encephalopathy/. Updated June 1, 2014. Accessed March 29, 2017.
  • 28. UpToDate. Lactulose: Drug Information. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/lactulose-drug-information. Last updated January 1, 2018. Accessed October 26, 2018.
  • 29. Devuni D. Hepatorenal Syndrome. In: Hepatorenal Syndrome. New York, NY: WebMD. http://emedicine.medscape.com/article/178208. Updated January 13, 2016. Accessed March 29, 2017.
  • 30. Runyon BA. Hepatorenal syndrome. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hepatorenal-syndrome. Last updated July 5, 2016. Accessed March 29, 2017.
  • 31. Said A. Portal Vein Obstruction. In: Portal Vein Obstruction. New York, NY: WebMD. http://emedicine.medscape.com/article/182425-overview. Updated December 27, 2016. Accessed March 29, 2017.
  • 32. Tendler DA, Lamont JT, Grubel P. Mesenteric venous thrombosis in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/mesenteric-venous-thrombosis-in-adults. Last updated July 18, 2016. Accessed March 29, 2017.
  • 33. Lv Y, Fan D. Hepatopulmonary Syndrome. Dig Dis Sci. 2015; 60(7): pp. 1914–1923. doi: 10.1007/s10620-015-3593-0.
  • 34. Saleemi S. Portopulmonary hypertension. Ann Thorac Med. 2010; 5(1): p. 5. doi: 10.4103/1817-1737.58953.
  • Ponziani FR. Portal vein thrombosis: Insight into physiopathology, diagnosis, and treatment. World Journal of Gastroenterology. 2010; 16(2): p. 143. doi: 10.3748/wjg.v16.i2.143.
  • Porres-Aguilar M, Altamirano JT, Torre-Delgadillo A, Charlton MR, Duarte-Rojo A. Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview. European Respiratory Review. 2012; 21(125): pp. 223–233. doi: 10.1183/09059180.00007211.
  • Grilo Bensusan I, Pascasio JM, Tirado JL, et al. The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation. Revista Española de Enfermedades Digestivas. 2017. doi: 10.17235/reed.2017.4219/2016.
  • Primignani M. Portal vein thrombosis, revisited. Digestive and Liver Disease. 2010; 42(3): pp. 163–170. doi: 10.1016/j.dld.2009.08.003.
  • Wu M, Schuster M, Tadros M. Update on Management of Portal Vein Thrombosis and the Role of Novel Anticoagulants. Journal of Clinical and Translational Hepatology. 2019; 7(X): pp. 1–11. doi: 10.14218/jcth.2018.00057.
  • Herold G. Internal Medicine. Cologne, Germany: Herold G; 2014.
  • Francoz C, Durand F, Kahn JA, Genyk YS, Nadim MK. Hepatorenal Syndrome. Clinical Journal of the American Society of Nephrology. 2019; 14(5): pp. 774–781. doi: 10.2215/cjn.12451018.
  • Ng CK, Chan MH, Tai MH, Lam CW. Hepatorenal syndrome. The Clinical biochemist. Reviews. 2007; 28(1): pp. 11–7. pmid: 17603637.
  • Mansour D, McPherson S. Management of decompensated cirrhosis. Clin Med. 2018; 18(Suppl 2): pp. s60–s65. doi: 10.7861/clinmedicine.18-2-s60.
  • Nusrat S. Cirrhosis and its complications: Evidence based treatment. World Journal of Gastroenterology. 2014; 20(18): p. 5442. doi: 10.3748/wjg.v20.i18.5442.
  • Centers for Disease Control and Prevention, National Center for Health Statistics. Underlying cause of death 1999-2018 on CDC WONDER online database. url: https://wonder.cdc.gov/controller/datarequest/D76;jsessionid=495356DBE5B2C9BD8DADE54EBFF7BD89 Accessed August 7, 2020.
  • Scaglione S1, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, Volk ML. The Epidemiology of Cirrhosis in the United States: A Population-based Study. Journal of Clinical Gastroenterology. 2015: pp. 690–696.
  • Tsoris A, Marlar CA. Use Of The Child Pugh Score In Liver Disease. StatPearls. 2020. pmid: 31194448.
last updated 09/09/2020
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