cirrhosis

File:Depiction of a Cirrhosis patient.png

Cirrhosis can take quite a long time to develop, and symptoms may be slow to emerge. Some early symptoms include tiredness, weakness, loss of appetite, weight loss, and nausea. Early signs may also include redness on the palms known as palmar erythema.{{Cite web |date=2024 |title=Cirrhosis of the liver |url=https://my.clevelandclinic.org/health/diseases/15572-cirrhosis-of-the-liver |access-date= |website=cleveland clinic}} People may also feel discomfort in the right upper abdomen around the liver.

As cirrhosis progresses, symptoms may include neurological changes affecting both the peripheral and central nervous systems, disrupting the neurotransmission within the brain and causing neuromuscular fatigue.{{Cite journal |last1=Bhandari |first1=Krishnagopal |last2=Kapoor |first2=Dharmesh |date=2022-03-01 |title=Fatigue in Cirrhosis |journal=Journal of Clinical and Experimental Hepatology |volume=12 |issue=2 |pages=617–624 |doi=10.1016/j.jceh.2021.08.028 |pmid=35535102 |pmc=9077229 |issn=0973-6883}} This can consist of cognitive impairments, confusion, memory loss, sleep disorders, and personality changes. Steatorrhea or presence of undigested fats in stool is also a symptom of cirrhosis.{{Cite journal |date=2024 |title=Steatorrhea in patients with liver disease |pmc=1931370 |journal=Canadian Medical Association Journal |volume=105 |issue=11 |pages=1143–1154 |pmid=5150072 | vauthors = Williams CN, Sidorov JJ }}

Worsening cirrhosis can cause a build-up of fluid in different parts of the body such as the legs (edema) and abdomen (ascites). Other signs of advancing disease include itchy skin, bruising easily, dark urine, and yellowing of the skin.

File:Cirrhosis liver.jpg

These features are a direct consequence of liver cells not functioning:

• Spider angiomata or spider nevi happen when there is dilatation of vasculature beneath the skin surface.{{cite book | vauthors = Samant H, Kothadia JP | chapter = Spider Angioma |date=2022 | chapter-url = http://www.ncbi.nlm.nih.gov/books/NBK507818/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29939595 |access-date=2022-03-14 }} There is a central, red spot with reddish extensions that radiate outward. This creates a visual effect that resembles a spider. It occurs in about one-third of cases. The likely cause is an increase in estrogen. Cirrhosis causes a rise of estrogen due to increased conversion of androgens into estrogen.{{cite journal | vauthors = Kur P, Kolasa-Wołosiuk A, Misiakiewicz-Has K, Wiszniewska B | title = Sex Hormone-Dependent Physiology and Diseases of Liver | journal = International Journal of Environmental Research and Public Health | volume = 17 | issue = 8 | pages = E2620 | date = April 2020 | pmid = 32290381 | pmc = 7216036 | doi = 10.3390/ijerph17082620 | doi-access = free }}
• Palmar erythema, a reddening of the palm below the thumb and little finger, is seen in about 23% of cirrhosis cases, and results from increased circulating estrogen levels.{{cite journal | vauthors = Serrao R, Zirwas M, English JC | title = Palmar erythema | journal = American Journal of Clinical Dermatology | volume = 8 | issue = 6 | pages = 347–56 | date = 2007 | pmid = 18039017 | doi = 10.2165/00128071-200708060-00004 | s2cid = 33297418 }}
• Gynecomastia, or the increase of breast size in men, is caused by increased estradiol (a potent type of estrogen).{{cite book | vauthors = Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Swerdloff RS, Ng CM | chapter = Gynecomastia: Etiology, Diagnosis, and Treatment |date=2000 | chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK279105/ | title = Endotext | veditors = Feingold KR, Anawalt B, Boyce A, Chrousos G |place=South Dartmouth (MA) |publisher=MDText.com, Inc. |pmid=25905330 |access-date=2022-03-16 }} This can occur in up to two-thirds of cases.{{cite book |title=Harrison's principles of internal medicine. |publisher=McGraw-Hill |year=2012 |isbn=978-0-07-174889-6 |veditors=Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J |edition=18th |location=New York |pages=Chapter 308. Cirrhosis and Its Complications}}
• Hypogonadism signifies a decreased functionality of the gonads.{{cite book | vauthors = Kim SM, Yalamanchi S, Dobs AS | chapter = Male Hypogonadism and Liver Disease |date=2017 | title = Male Hypogonadism |pages=219–234 | veditors = Winters SJ, Huhtaniemi IT |place=Cham |publisher=Springer International Publishing |doi=10.1007/978-3-319-53298-1_11 |isbn=978-3-319-53296-7 }} This can result in impotence, infertility, loss of sexual drive, and testicular atrophy. A swollen scrotum may also be evident.{{Cite journal | vauthors = Qi X, An S, Li H, Guo X |date=2017-08-24 |title=Recurrent scrotal edema in liver cirrhosis |url=http://amj.amegroups.com/article/view/4005/4730 |journal=AME Medical Journal |volume=2 |pages=124 |doi=10.21037/amj.2017.08.22 |doi-access=free |url-access=subscription }}
• Liver size can be enlarged, normal, or shrunken in people with cirrhosis.{{cite journal |vauthors=Plauth M, Schütz ET |date=September 2002 |title=Cachexia in liver cirrhosis |journal=International Journal of Cardiology |volume=85 |issue=1 |pages=83–87 |doi=10.1016/s0167-5273(02)00236-x |pmid=12163212}} As the disease progresses, the liver will typically shrink due to the result of scarring.{{cite web | vauthors = Jeffrey G |date=7 October 2021 |title=Cirrhosis of the Liver |website=emedicinehealth |url=https://www.emedicinehealth.com/cirrhosis/article_em.htm |access-date=15 March 2022}}
• Jaundice is the yellowing of the skin. It can additionally cause yellowing of mucous membranes notably of the white of the eyes. This phenomenon is due to increased levels of bilirubin, which may also cause the urine to be dark-colored.{{cite web |title=Jaundice - Hepatic and Biliary Disorders |url=https://www.merckmanuals.com/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice |access-date=2022-03-16 |website=Merck Manuals Professional Edition}}

File:Cirrhosis.webm

Liver cirrhosis makes it hard for blood to flow in the portal venous system.{{cite web |title=Portal Hypertension |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/portal-hypertension |access-date=2022-03-16 |publisher=www.hopkinsmedicine.org}} This resistance creates a backup of blood and increases pressure. This results in portal hypertension. Effects of portal hypertension include:

• Ascites is a build-up of fluid in the peritoneal cavity in the abdomen
• An enlarged spleen in 35–50% of cases
• Esophageal varices and gastric varices result from collateral circulation in the esophagus and stomach (a process called portacaval anastomosis).{{cite book | vauthors = Meseeha M, Attia M | chapter = Esophageal Varices |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK448078/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28846255 |access-date=2022-03-16 }} When the blood vessels in this circulation become enlarged, they are called varices. Varices are more likely to rupture at this point. Variceal rupture often leads to severe bleeding, which can be fatal.
• Caput medusae are dilated paraumbilical collateral veins due to portal hypertension. Blood from the portal venous system may be forced through the paraumbilical veins and ultimately to the abdominal wall veins. File:ఉదరకుడ్యంలో ఉబ్బుసిరలు ( Caput Medusae ).jpeg The created pattern resembles the head of Medusa, hence the name.
• Cruveilhier-Baumgarten bruit is bruit in the epigastric region (on examination by stethoscope).{{cite journal | vauthors = Masoodi I, Farooq O, Singh R, Ahmad N, Bhat M, Wani A | title = Courveilhier baumgarten syndrome: a rare syndrome revisited | journal = International Journal of Health Sciences | volume = 3 | issue = 1 | pages = 97–99 | date = January 2009 | pmid = 21475517 | pmc = 3068787 }} It is due to extra connections forming between the portal system and the paraumbilical veins.

Some signs that may be present include changes in the nails (such as Muehrcke's lines, Terry's nails, and nail clubbing).{{cite journal | vauthors = Witkowska AB, Jasterzbski TJ, Schwartz RA | title = Terry's Nails: A Sign of Systemic Disease | journal = Indian Journal of Dermatology | volume = 62 | issue = 3 | pages = 309–311 | date = 2017 | pmid = 28584375 | pmc = 5448267 |doi = 10.4103/ijd.IJD_98_17 |doi-access=free}}{{Cite journal | vauthors = Abd El Meged MM |date=2019-04-01 |title=Patterns of nail changes in chronic liver diseases |journal=Sohag Medical Journal |volume=23 |issue=2 |pages=166–170 |doi=10.21608/smj.2019.47672 |s2cid=203813520 |issn=1687-8353|doi-access=free }} Additional changes may be seen in the hands (Dupuytren's contracture) as well as the skin/bones (hypertrophic osteoarthropathy).

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

• Bruising and bleeding can result from decreased production of blood clotting factors.{{Cite book | vauthors = Friedman L |title=Handbook of Liver Disease, 4e |publisher=Elsevier |year=2018 |isbn=978-0-323-47874-8}}
• Hepatic encephalopathy (HE) occurs when ammonia and related substances build up in the blood. This build-up affects brain function when they are not cleared from the blood by the liver. Symptoms can include unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits, or psychosis. One classic physical examination finding is asterixis. This is the asynchronous flapping of outstretched, dorsiflexed hands. Fetor hepaticus is a musty breath odor resulting from increased dimethyl sulfide and is a feature of HE.{{cite web |vauthors=Brennan D |title=What Is Fetor Hepaticus? |url=https://www.webmd.com/a-to-z-guides/what-is-fetor-hepaticus |access-date=2022-03-17 |website=WebMD}}
• Increased sensitivity to medication can be caused by decreased metabolism of the active compounds.{{Cite web |last=Alabama |first=Jennifer A. Gentile, PharmD Candidate 2021 Logan B. Boone, PharmD Candidate 2021 Samford University McWhorter School of Pharmacy Birmingham, Alabama Jeffrey A. Kyle, PharmD, BCPS Professor of Pharmacy Practice Samford University McWhorter School of Pharmacy Birmingham, Alabama Langley R. Kyle, PharmD Clinical Pharmacy Specialist RxBenefits Birmingham |title=Drug Considerations for Medication Therapy in Cirrhosis |url=https://www.uspharmacist.com/article/drug-considerations-for-medication-therapy-in-cirrhosis |access-date=2024-11-08 |website=www.uspharmacist.com |language=en}}
• Acute kidney injury (particularly hepatorenal syndrome).
• Cachexia associated with muscle wasting and weakness.

Cirrhosis has many possible causes, and more than one cause may be present. History taking is of importance in trying to determine the most likely cause. Globally, 57% of cirrhosis is attributable to either hepatitis B (30%) or hepatitis C (27%).{{cite journal | vauthors = Samji NS, Buggs AM, Roy PK | journal = Medscape | publisher = WebMD LLC. |date=2021-10-17 | veditors = Anand BS |title=Viral Hepatitis: Background, Pathophysiology, Etiology |url=https://emedicine.medscape.com/article/775507-overview}}{{cite journal | vauthors = Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP | title = The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide | journal = Journal of Hepatology | volume = 45 | issue = 4 | pages = 529–538 | date = October 2006 | pmid = 16879891 | doi = 10.1016/j.jhep.2006.05.013 }} Alcohol use disorder is another major cause, accounting for about 20–40% of the cases.

File:Hepatitis C.jpg viral particles and the liver]]

• Alcoholic liver disease (ALD, or alcoholic cirrhosis) develops for 10–20% of individuals who drink heavily for a decade or more.{{cite web |title=Cirrhosis of the Liver |url=https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/cirrhosis/ |access-date=2022-03-17 |website=American Liver Foundation}} Alcohol seems to injure the liver by blocking the normal metabolism of protein, fats, and carbohydrates. This injury happens through the formation of acetaldehyde from alcohol. Acetaldehyde is reactive and leads to the accumulation of other reactive products in the liver. People with ALD may also have concurrent alcoholic hepatitis. Associated symptoms are fever, hepatomegaly, jaundice, and anorexia.{{cite journal | vauthors = Stickel F, Datz C, Hampe J, Bataller R | title = Pathophysiology and Management of Alcoholic Liver Disease: Update 2016 | journal = Gut and Liver | volume = 11 | issue = 2 | pages = 173–188 | date = March 2017 | pmid = 28274107 | pmc = 5347641 | doi = 10.5009/gnl16477 }} AST and ALT blood levels are both elevated, but at less than 300 IU/liter, with an AST:ALT ratio > 2.0, a value rarely seen in other liver diseases.{{cite book |title=Current medical diagnosis and treatment 2014. |vauthors=Friedman LS |publisher=Mcgraw-Hill |year=2014 |isbn=978-0-07-180633-6 |location=[S.l.] |pages=Chapter 16. Liver, Biliary Tract, & Pancreas Disorders}} In the United States, 40% of cirrhosis-related deaths are due to alcohol.
• In non-alcoholic fatty liver disease (NAFLD), fat builds up in the liver and eventually causes scar tissue.{{Cite book | vauthors = Machado MV, Diehl AM | chapter = Pathogenesis of Nonalcoholic Fatty Liver Disease | pages = 369–390 | veditors = Sanyal AJ, Boyer TD, Terrault NA, Lindor KD |date=2018 |title=Zakim and Boyer's Hepatology |doi=10.1016/c2013-0-19055-1| isbn = 978-0-323-37591-7 }} This type of disorder can be caused by obesity, diabetes, malnutrition, coronary artery disease, and steroids.{{cite journal | vauthors = Golabi P, Paik JM, Arshad T, Younossi Y, Mishra A, Younossi ZM | title = Mortality of NAFLD According to the Body Composition and Presence of Metabolic Abnormalities | journal = Hepatology Communications | volume = 4 | issue = 8 | pages = 1136–1148 | date = August 2020 | pmid = 32766474 | pmc = 7395070 | doi = 10.1002/hep4.1534 }} Though similar in signs to alcoholic liver disease, no history of notable alcohol use is found. Blood tests and medical imaging are used to diagnose NAFLD and NASH, and sometimes a liver biopsy is needed.{{cite web |title=Diagnosis of NAFLD & NASH {{!}} NIDDK |url=https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/diagnosis |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=9 March 2021 |archive-date=4 March 2021 |archive-url=https://web.archive.org/web/20210304223353/https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/diagnosis |url-status=live }}
• Chronic hepatitis C, an infection with the hepatitis C virus, causes inflammation of the liver and a variable grade of damage to the organ. Over several decades, this inflammation and damage can lead to cirrhosis. Among people with chronic hepatitis C, 20–30% develop cirrhosis. Cirrhosis caused by hepatitis C and alcoholic liver disease are the most common reasons for liver transplant. Both hepatitis C and hepatitis B–related cirrhosis can also be attributed with heroin addiction.{{cite news|url=https://bedrockrecoverycenter.com/addiction/heroin/health-conditions/|title=Heroin Addiction Health Conditions|publisher=Bedrock Recovery Center|accessdate=August 7, 2022}}
• Chronic hepatitis B causes liver inflammation and injury that over several decades can lead to cirrhosis. Hepatitis D is dependent on the presence of hepatitis B and accelerates cirrhosis in co-infection.

• In primary biliary cholangitis (previously known as primary biliary cirrhosis), the bile ducts become damaged by an autoimmune process. This leads to liver damage. Some people may have no symptoms, while others may present with fatigue, pruritus, or skin hyperpigmentation. The liver is typically enlarged which is referred to as hepatomegaly.{{cite web |title=Primary Biliary Cholangitis: Symptoms, Causes, Treatments |url=https://my.clevelandclinic.org/health/diseases/17715-primary-biliary-cholangitis-pbc- |access-date=2022-03-17 |website=Cleveland Clinic}} Rises in alkaline phosphatase, cholesterol, and bilirubin levels occur. Patients are usually positive for anti-mitochondrial antibodies.
• Primary sclerosing cholangitis is a disorder of the bile ducts that presents with pruritus, steatorrhea, fat-soluble vitamin deficiencies, and metabolic bone disease. A strong association with inflammatory bowel disease is seen, especially ulcerative colitis.
• Autoimmune hepatitis is caused by an attack of the liver by lymphocytes. This causes inflammation and eventually scarring as well as cirrhosis. Findings include elevations in serum globulins, especially gamma globulins.
• Hereditary hemochromatosis usually presents with skin hyperpigmentation, diabetes mellitus, pseudogout, or cardiomyopathy. All of these are due to signs of iron overload. Family history of cirrhosis is common as well.
• Wilson's disease is an autosomal recessive disorder characterized by low ceruloplasmin in the blood and increased copper of the liver. Copper in the urine is also elevated. People with Wilson's disease may also have Kayser–Fleischer rings in the cornea and altered mental status.
• Indian childhood cirrhosis is a form of neonatal cholestasis characterized by deposition of copper in the liver{{cite book | vauthors = Coenen IC, Houwen RH | chapter = Indian childhood cirrhosis and other disorders of copper handling. | title = Clinical and Translational Perspectives on Wiloson Disease | date = January 2019 | pages = 449–453 | publisher = Academic Press | doi = 10.1016/B978-0-12-810532-0.00044-6 | isbn = 978-0-12-810532-0 | s2cid = 80994882 }}
• Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder of low levels of the enzyme alpha-1 antitrypsin
• Cardiac cirrhosis is due to chronic right-sided heart failure, which leads to liver congestion
• Galactosemia{{cite web | vauthors = Oiseth S, Jones L, Maza E |url= https://www.lecturio.com/concepts/galactosemia/ | title= Galactosemia |website=The Lecturio Medical Concept Library |access-date= 15 August 2021}}
• Glycogen storage disease type IV
• Cystic fibrosis
• Hepatotoxic drugs or toxins, such as acetaminophen (paracetamol), methotrexate, or amiodarone

The liver plays a vital role in many metabolic processes in the body including protein synthesis, detoxification, nutrient storage (such as glycogen), platelet production and clearance of bilirubin. With progressive liver damage, hepatocyte death and replacement of functional liver tissue with fibrosis in cirrhosis, these processes are disrupted. This leads to many of the metabolic derangements and symptoms seen in cirrhosis.{{cite journal |last1=Tapper |first1=Elliot B. |last2=Parikh |first2=Neehar D. |title=Diagnosis and Management of Cirrhosis and Its Complications: A Review |journal=JAMA |date=9 May 2023 |volume=329 |issue=18 |pages=1589–1602 |doi=10.1001/jama.2023.5997|pmid=37159031 |pmc=10843851 }}

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 fully reversible.{{citation needed|date=April 2022}}

The pathological hallmark of cirrhosis is the development of scar tissue that replaces normal tissue, which is normally organized into lobules. This scar tissue blocks the portal flow of blood through the organ, raising the blood pressure. This manifests as portal hypertension in which the pressure gradient between the portal circulation as compared to the systemic circulation is elevated. This portal hypertension leads to decreased sinusoidal flow from liver cells to nearby sinusoids in the liver, and increased lymph production with extravasation of lymph to the extracellular space, causing ascites. This also causes reduced cardiac return and central blood volume, which activates the renin-angiotensin system (RAAS) which causes kidneys to reabsorb sodium and water, causing water retention and further ascites. Activation of the RAAS also causes kidney vasoconstriction and may cause kidney injury.

Research has shown the pivotal role of the stellate cell, that normally stores vitamin A, in the development of cirrhosis. Damage to the liver tissue from inflammation leads to the activation of stellate cells, which increases fibrosis through the production of myofibroblasts, and obstructs hepatic blood flow.{{cite book | veditors = Hammer GD, McPhee SJ |title=Pathophysiology of disease : an introduction to clinical medicine |year=2010 |publisher=McGraw-Hill Medical |location=New York |isbn=978-0-07-162167-0 |pages=Chapter 14: Liver Disease. Cirrhosis |edition=6th}} In addition, stellate cells secrete TGF beta 1, which leads to a fibrotic response and proliferation of connective tissue. TGF-β1 have been implicated in the process of activating hepatic stellate cells (HSCs) with the magnitude of fibrosis being in proportion to increase in TGF β levels. ACTA2 is associated with TGF β pathway that enhances contractile properties of HSCs leading to fibrosis.{{cite journal | vauthors = Hassan S, Shah H, Shawana S | title = Dysregulated epidermal growth factor and tumor growth factor-beta receptor signaling through GFAP-ACTA2 protein interaction in liver fibrosis | journal = Pakistan Journal of Medical Sciences | volume = 36 | issue = 4 | pages = 782–787 | year = 2020 | pmid = 32494274 | pmc = 7260937 | doi = 10.12669/pjms.36.4.1845 }} Furthermore, HSCs secrete TIMP1 and TIMP2, naturally occurring inhibitors of matrix metalloproteinases (MMPs), which prevent MMPs from breaking down the fibrotic material in the extracellular matrix.{{cite journal | vauthors = Iredale JP | title = Cirrhosis: new research provides a basis for rational and targeted treatments | journal = BMJ | volume = 327 | issue = 7407 | pages = 143–147 | date = July 2003 | pmid = 12869458 | pmc = 1126509 | doi = 10.1136/bmj.327.7407.143 | url = http://bmj.bmjjournals.com/cgi/content/full/327/7407/143 | url-status = live | archive-url = https://web.archive.org/web/20041029175310/http://bmj.bmjjournals.com/cgi/content/full/327/7407/143 | archive-date = 2004-10-29 }}{{cite journal | vauthors = Puche JE, Saiman Y, Friedman SL | title = Hepatic stellate cells and liver fibrosis | journal = Comprehensive Physiology | volume = 3 | issue = 4 | pages = 1473–1492 | date = October 2013 | pmid = 24265236 | doi = 10.1002/cphy.c120035 | isbn = 978-0-470-65071-4 }}

As this cascade of processes continues, fibrous tissue bands (septa) separate hepatocyte nodules, which eventually replace the entire liver architecture, leading to decreased blood flow throughout. The spleen becomes congested, and enlarged, resulting in its retention of platelets, which are needed for normal blood clotting. Portal hypertension is responsible for the most severe complications of cirrhosis.{{citation needed|date=April 2022}}

File:Caudate lobe hypertrophy 0001.jpg hypertrophy on ultrasound due to cirrhosis]]

File:Hepatofugal flow in portal vein.jpg]]

The diagnosis of cirrhosis in an individual is based on multiple factors. Cirrhosis may be suspected from laboratory findings, physical exam, and the person's medical history. Imaging is generally obtained to evaluate the liver. A liver biopsy will confirm the diagnosis; however, is generally not required.

Ultrasound is routinely used in the evaluation of cirrhosis. It may show a small and shrunken liver in advanced disease. On ultrasound, there is increased echogenicity with irregular appearing areas.{{cite journal | vauthors = Wu M, Sharma PG, Grajo JR | title = The Echogenic Liver: Steatosis and Beyond | journal = Ultrasound Quarterly | volume = 37 | issue = 4 | pages = 308–314 | date = September 2020 | pmid = 32956242 | doi = 10.1097/RUQ.0000000000000510 | s2cid = 221842327 }} Other suggestive findings are an enlarged caudate lobe, liver surface nodularity{{Cite journal |last1=Costantino |first1=Andrea |last2=Piagnani |first2=Alessandra |last3=Nandi |first3=Nicoletta |last4=Sciola |first4=Valentina |last5=Maggioni |first5=Marco |last6=Donato |first6=Francesca |last7=Vecchi |first7=Maurizio |last8=Lampertico |first8=Pietro |last9=Casazza |first9=Giovanni |last10=Fraquelli |first10=Mirella |date=2022 |title=Reproducibility and diagnostic accuracy of pocket-sized ultrasound devices in ruling out compensated cirrhosis of mixed etiology |journal=European Radiology |volume=32 |issue=7 |pages=4609–4615 |doi=10.1007/s00330-022-08572-2 |pmc=9213370 |pmid=35238968}} widening of the fissures and enlargement of the spleen.{{cite journal | vauthors = Yeom SK, Lee CH, Cha SH, Park CM | title = Prediction of liver cirrhosis, using diagnostic imaging tools | journal = World Journal of Hepatology | volume = 7 | issue = 17 | pages = 2069–2079 | date = August 2015 | pmid = 26301049 | pmc = 4539400 | doi = 10.4254/wjh.v7.i17.2069 | doi-access = free }} An enlarged spleen, which normally measures less than {{Cvt|11-12|cm}} in adults, may suggest underlying portal hypertension.Chapman J, Goyal A, Azevedo AM. Splenomegaly. [Updated 2021 Aug 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: [https://www.ncbi.nlm.nih.gov/books/NBK430907/] Ultrasound may also screen for hepatocellular carcinoma and portal hypertension. This is done by assessing flow in the hepatic vein. An increased portal vein pulsatility may be seen. However, this may be a sign of elevated right atrial pressure.{{cite journal | vauthors = Berzigotti A, Seijo S, Reverter E, Bosch J | title = Assessing portal hypertension in liver diseases | journal = Expert Review of Gastroenterology & Hepatology | volume = 7 | issue = 2 | pages = 141–155 | date = February 2013 | pmid = 23363263 | doi = 10.1586/egh.12.83 | s2cid = 31057915 | doi-access = free }} Portal vein pulsatility are usually measured by a pulsatility indices (PI). A number above a certain values indicates cirrhosis (see table below).

The best predictors of cirrhosis are ascites, platelet count < 160,000/mm³, spider angiomata, and a Bonacini cirrhosis discriminant score greater than 7 (as the sum of scores for platelet count, ALT/AST ratio and INR as per table).{{cite journal |vauthors=Udell JA, Wang CS, Tinmouth J, FitzGerald JM, Ayas NT, Simel DL, Schulzer M, Mak E, Yoshida EM |date=February 2012 |title=Does this patient with liver disease have cirrhosis? |journal=JAMA |volume=307 |issue=8 |pages=832–842 |doi=10.1001/jama.2012.186 |pmid=22357834}}

These findings are typical in cirrhosis:

• Thrombocytopenia, typically multifactorial, is due to alcoholic marrow suppression, sepsis, lack of folate, platelet sequestering in the spleen, and decreased thrombopoietin. However, this rarely results in a platelet count < 50,000/mL.{{cite book |title=Schiff's diseases of the liver. |publisher=John Wiley & Sons |year=1999 |isbn=978-0-470-65468-2 |veditors=Maddrey WC, Schiff ER, Sorrell MF |edition=11th |location=Chichester, West Sussex, UK |pages=Evaluation of the Liver A: Laboratory Test}}
• Aminotransferases AST and ALT are moderately elevated, with AST > ALT. However, normal aminotransferase levels do not preclude cirrhosis.
• Alkaline phosphatase – slightly elevated but less than 2–3 times the upper limit of normal.{{citation needed|date=September 2022}}
• Gamma-glutamyl transferase – correlates with AP levels. Typically much higher in chronic liver disease from alcohol.
• Bilirubin levels are normal when compensated, but may elevate as cirrhosis progresses.{{citation needed|date=September 2022}}
• Albumin levels fall as the synthetic function of the liver declines with worsening cirrhosis since albumin is exclusively synthesized in the liver.
• Prothrombin time increases, since the liver synthesizes clotting factors.
• Globulins increase due to shunting of bacterial antigens away from the liver to lymphoid tissue.
• Serum sodium levels fall (hyponatremia) due to inability to excrete free water resulting from high levels of ADH and aldosterone.
• Leukopenia and neutropenia are due to splenomegaly with splenic margination.{{citation needed|date=September 2022}}
• Coagulation defects occur, as the liver produces most of the coagulation factors, thus coagulopathy correlates with worsening liver disease.
• Glucagon is increased in cirrhosis.
• Vasoactive intestinal peptide is increased as blood is shunted into the intestinal system because of portal hypertension.
• Vasodilators are increased (such as nitric oxide and carbon monoxide) reducing afterload with compensatory increase in cardiac output, mixed venous oxygen saturation.{{cite book |title=Current practice guidelines in primary care 2013 |vauthors=Slater JS, Esherick DS, Clark ED |date=2012-12-18 |publisher=McGraw-Hill Medical |isbn=978-0-07-179750-4 |location=New York |pages=Chapter 3: Disease Management}}
• Renin is increased (as well as sodium retention in kidneys) secondary to a fall in systemic vascular resistance.{{cite journal |vauthors=Van Thiel DH, Gavaler JS, Schade RR |date=February 1985 |title=Liver disease and the hypothalamic pituitary gonadal axis |journal=Seminars in Liver Disease |volume=5 |issue=1 |pages=35–45 |doi=10.1055/s-2008-1041756 |pmid=3983651|s2cid=35436861 }}

FibroTest is a biomarker for fibrosis that may be used instead of a biopsy.{{cite journal |vauthors=Halfon P, Munteanu M, Poynard T |date=September 2008 |title=FibroTest-ActiTest as a non-invasive marker of liver fibrosis |journal=Gastroenterologie Clinique et Biologique |volume=32 |issue=6 Suppl 1 |pages=22–39 |doi=10.1016/S0399-8320(08)73991-5 |pmid=18973844}}

Other laboratory studies performed in newly diagnosed cirrhosis may include:

• Serology for hepatitis viruses, autoantibodies (ANA, anti-smooth muscle, antimitochondria, anti-LKM)
• Ferritin{{cite journal |vauthors=Tornai D, Antal-Szalmas P, Tornai T, Papp M, Tornai I, Sipeki N, Janka T, Balogh B, Vitalis Z |date=March 2021 |title=Abnormal ferritin levels predict development of poor outcomes in cirrhotic outpatients: a cohort study |journal=BMC Gastroenterology |volume=21 |issue=1 |page=94 |doi=10.1186/s12876-021-01669-w |pmc=7923668 |pmid=33653274 |doi-access=free }}{{cite journal |vauthors=Maiwall R, Kumar S, Chaudhary AK, Maras J, Wani Z, Kumar C, Rastogi A, Bihari C, Vashisht C, Sarin SK |date=July 2014 |title=Serum ferritin predicts early mortality in patients with decompensated cirrhosis |journal=Journal of Hepatology |volume=61 |issue=1 |pages=43–50 |doi=10.1016/j.jhep.2014.03.027 |pmid=24681346}} and transferrin saturation: markers of iron overload as in hemochromatosis, copper and ceruloplasmin: markers of copper overload as in Wilson's disease
• Immunoglobulin levels (IgG, IgM, IgA) – these immunoglobins are nonspecific, but may help in distinguishing various causes.
• IgG level is elevated in chronic hepatitis, alcoholic and autoimmune hepatitis. It's slow and sustained increase is seen in viral hepatitis.
• IgM significantly increased in primary biliary cirrhosis and moderately increased in viral hepatitis and cirrhosis.
• IgA is increased in alcoholic cirrhosis and primary biliary cirrhosis.{{cn|date=April 2024}}
• Cholesterol and glucose
• Alpha 1-antitrypsin

Markers of inflammation and immune cell activation are typically elevated in cirrhotic patients, especially in the decompensated disease stage:

• C-reactive protein (CRP){{cite journal |vauthors=Papp M, Vitalis Z, Altorjay I, Tornai I, Udvardy M, Harsfalvi J, Vida A, Kappelmayer J, Lakatos PL, Antal-Szalmas P |date=April 2012 |title=Acute phase proteins in the diagnosis and prediction of cirrhosis associated bacterial infections |url=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1478-3231.2011.02689.x |url-status=live |journal=Liver International |volume=32 |issue=4 |pages=603–611 |doi=10.1111/j.1478-3231.2011.02689.x |pmid=22145664 |archive-url=https://web.archive.org/web/20210425103201/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1478-3231.2011.02689.x |archive-date=2021-04-25 |access-date=2021-04-25 |s2cid=10326820}}
• Procalcitonin (PCT)
• Presepsin{{cite journal |vauthors=Papp M, Tornai T, Vitalis Z, Tornai I, Tornai D, Dinya T, Sumegi A, Antal-Szalmas P |date=November 2016 |title=Presepsin teardown - pitfalls of biomarkers in the diagnosis and prognosis of bacterial infection in cirrhosis |journal=World Journal of Gastroenterology |volume=22 |issue=41 |pages=9172–9185 |doi=10.3748/wjg.v22.i41.9172 |pmc=5107598 |pmid=27895404 |doi-access=free }}
• soluble CD14
• soluble CD163{{cite journal |vauthors=Tornai T, Vitalis Z, Sipeki N, Dinya T, Tornai D, Antal-Szalmas P, Karanyi Z, Tornai I, Papp M |date=November 2016 |title=Macrophage activation marker, soluble CD163, is an independent predictor of short-term mortality in patients with cirrhosis and bacterial infection |url=https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13133 |url-status=live |journal=Liver International |volume=36 |issue=11 |pages=1628–1638 |doi=10.1111/liv.13133 |pmid=27031405 |archive-url=https://web.archive.org/web/20210425103201/https://onlinelibrary.wiley.com/doi/abs/10.1111/liv.13133 |archive-date=2021-04-25 |access-date=2021-04-25 |hdl-access=free |s2cid=206174528 |hdl=2437/223046}}
• soluble CD206 (mannose receptor){{cite journal |vauthors=Laursen TL, Rødgaard-Hansen S, Møller HJ, Mortensen C, Karlsen S, Nielsen DT, Frevert S, Clemmesen JO, Møller S, Jensen JS, Bendtsen F, Grønbaek H |date=April 2017 |title=The soluble mannose receptor is released from the liver in cirrhotic patients, but is not associated with bacterial translocation |journal=Liver International |volume=37 |issue=4 |pages=569–575 |doi=10.1111/liv.13262 |pmid=27706896 |s2cid=46856702}}
• soluble TREM-1{{cite journal |vauthors=Tornai D, Vitalis Z, Jonas A, Janka T, Foldi I, Tornai T, Sipeki N, Csillag A, Balogh B, Sumegi A, Foldesi R, Papp M, Antal-Szalmas P |date=September 2021 |title=Increased sTREM-1 levels identify cirrhotic patients with bacterial infection and predict their 90-day mortality |journal=Clinics and Research in Hepatology and Gastroenterology |volume=45 |issue=5 |page=101579 |doi=10.1016/j.clinre.2020.11.009 |pmid=33773436 |doi-access=free}}

The link between gut microbiota constitution and liver health (Particularly in Cirrhosis) has been well described,{{Cite journal |last1=Zhu |first1=Xiaofei |last2=Zhou |first2=Ziyuan |last3=Pan |first3=Xiaxia |date=2024-03-14 |title=Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001–2023) |journal=Frontiers in Microbiology |language=English |volume=15 |doi=10.3389/fmicb.2024.1342356 |doi-access=free |issn=1664-302X |pmc=10972893 |pmid=38550860}} however specific biomarkers for prediction of Cirrhosis still requires further research. A 2014 study identified 15 microbial biomarkers from the gut microbiota.{{cite journal | vauthors = Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, Zhou J, Ni S, Liu L, Pons N, Batto JM, Kennedy SP, Leonard P, Yuan C, Ding W, Chen Y, Hu X, Zheng B, Qian G, Xu W, Ehrlich SD, Zheng S, Li L | title = Alterations of the human gut microbiome in liver cirrhosis | journal = Nature | volume = 513 | issue = 7516 | pages = 59–64 | date = September 2014 | pmid = 25079328 | doi = 10.1038/nature13568 | bibcode = 2014Natur.513...59Q | s2cid = 205239766 }} These could potentially be used to discriminate patients with liver cirrhosis from healthy individuals.

File:Cirrhosis high mag.jpg showing cirrhosis, trichrome stain]]

The gold standard for diagnosis of cirrhosis is a liver biopsy. This is usually carried out as a fine-needle approach, through the skin (percutaneous), or internal jugular vein (transjugular).{{cite journal |vauthors=McCarty TR, Bazarbashi AN, Njei B, Ryou M, Aslanian HR, Muniraj T |date=September 2020 |title=Endoscopic Ultrasound-Guided, Percutaneous, and Transjugular Liver Biopsy: A Comparative Systematic Review and Meta-Analysis |journal=Clinical Endoscopy |volume=53 |issue=5 |pages=583–593 |doi=10.5946/ce.2019.211 |pmc=7548145 |pmid=33027584 |doi-access=free}} Endoscopic ultrasound-guided liver biopsy (EUS), using the percutaneous or transjugular route, has become a good alternative to use.{{cite journal |vauthors=Mok SR, Diehl DL |date=January 2019 |title=The Role of EUS in Liver Biopsy |journal=Current Gastroenterology Reports |volume=21 |issue=2 |page=6 |doi=10.1007/s11894-019-0675-8 |pmid=30706151 |s2cid=73440352}} EUS can target liver areas that are widely separated,{{cite journal |vauthors=Diehl DL |date=April 2019 |title=Endoscopic Ultrasound-guided Liver Biopsy |journal=Gastrointestinal Endoscopy Clinics of North America |volume=29 |issue=2 |pages=173–186 |doi=10.1016/j.giec.2018.11.002 |pmc=6383155 |pmid=30846147}} and can deliver bi-lobar biopsies. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest cirrhosis. Furthermore, a small but significant risk of complications is associated with liver biopsy, and cirrhosis itself predisposes for complications caused by liver biopsy.{{cite journal |vauthors=Grant A, Neuberger J |date=October 1999 |title=Guidelines on the use of liver biopsy in clinical practice. British Society of Gastroenterology |url=http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1 |url-status=live |journal=Gut |volume=45 |issue=Suppl 4 |pages=IV1–IV11 |doi=10.1136/gut.45.2008.iv1 |pmc=1766696 |pmid=10485854 |archive-url=https://web.archive.org/web/20070630073451/http://gut.bmj.com/cgi/content/full/45/suppl_4/IV1 |archive-date=2007-06-30 |quote=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.}}

Once the biopsy is obtained, a pathologist will study the sample. Cirrhosis is defined by its 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 on 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.{{cite book | vauthors = Brenner D, Rippe RA |chapter=Pathogenesis of Hepatic Fibrosis |title=Textbook of Gastroenterology | veditors = Yamada | editor-link1 = Tadataka Yamada |edition=4th |volume=2 |year=2003 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-2861-4}}

File:Histopathology of mild zone 3 steatosis without fibrosis (van Gieson).jpg|No fibrosis, but mild zone 3 steatosis, in which collagen fibres (pink–red, arrow) are confined to portal tracts (P) (Van Gieson's stain){{cite journal | vauthors = Boyd A, Cain O, Chauhan A, Webb GJ |title=Medical liver biopsy: background, indications, procedure and histopathology |journal=Frontline Gastroenterology |volume=11 |issue=1 |year=2020 |pages=40–47 |issn=2041-4137 |doi=10.1136/flgastro-2018-101139 |pmid=31885839 |pmc=6914302}}
-"This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license"

File:Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (van Gieson).jpg|Histopathology of steatohepatitis with mild fibrosis in the form of fibrous expansion (Van Gieson's stain)

File:Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (van Gieson).jpg|Histopathology of steatohepatitis with moderate fibrosis, with thin fibrous bridges (Van Gieson's stain)

File:Histopathology of steatohepatitis with established cirrhosis, with thick bands of fibrosis (van Gieson).jpg|Histopathology of steatohepatitis with established cirrhosis, with thick bands of fibrosis (Van Gieson's stain)

File:Cirrhosis of the liver (trichrome stain) (5690946257).jpg|Trichrome stain, showing cirrhosis as a nodular texture surrounded by fibrosis (wherein collagen is stained blue).

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. In congestive hepatopathy there are erythrocytes and a greater amount of fibrosis in the tissue surrounding the hepatic veins.{{cite journal | vauthors = Giallourakis CC, Rosenberg PM, Friedman LS | title = The liver in heart failure | journal = Clinics in Liver Disease | volume = 6 | issue = 4 | pages = 947–67, viii–ix | date = November 2002 | pmid = 12516201 | doi = 10.1016/S1089-3261(02)00056-9 }} In primary biliary cholangitis, there is fibrosis around the bile duct, the presence of granulomas and pooling of bile.{{cite journal | vauthors = Heathcote EJ | title = Primary biliary cirrhosis: historical perspective | journal = Clinics in Liver Disease | volume = 7 | issue = 4 | pages = 735–740 | date = November 2003 | pmid = 14594128 | doi = 10.1016/S1089-3261(03)00098-9 }} Lastly in alcoholic cirrhosis, there is infiltration of the liver with neutrophils.

Macroscopically, the liver is initially enlarged, but with the progression of the disease, it becomes smaller. Its surface is irregular, the consistency is firm, and if associated with steatosis the color is yellow. Depending on the size of the nodules, there are three macroscopic types: micronodular, macronodular, and mixed cirrhosis. In the 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. Mixed cirrhosis consists of nodules of different sizes.{{cite book | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK482419/ | chapter = Hepatic Cirrhosis |vauthors=Bashar S, Savio J | title = StatPearls |publisher=StatPearls |year=2020 | pmid = 29494026 |access-date=2019-11-11 |archive-url=https://web.archive.org/web/20200903005535/https://www.ncbi.nlm.nih.gov/books/NBK482419/ |archive-date=2020-09-03 |url-status=live}}

File:Gross pathology of alcoholic liver cirrhosis.jpg|Micronodular cirrhosis, with diffuse areas of pallor

File:Wątroba marska (Ultima Thule).jpg|Pale macronodules of cirrhosis

File:Hepatocellular carcinoma 1.jpg|Cirrhosis leading to hepatocellular carcinoma

The severity of cirrhosis is commonly classified with the Child–Pugh score (also known as the Child–Pugh–Turcotte score).{{cite book | vauthors = Tsoris A, Marlar CA | chapter = Use Of The Child Pugh Score In Liver Disease |date=2022 |url=http://www.ncbi.nlm.nih.gov/books/NBK542308/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31194448 |access-date=2022-03-23 }} This system was devised in 1964 by Child and Turcotte, and modified in 1973 by Pugh and others.{{Cite web |vauthors=Shakerdge K |title=What Are the MELD and Child-Pugh Scores for Liver Disease? |url=https://www.webmd.com/hepatitis/meld-score-for-liver-disease |access-date=2022-03-23 |website=WebMD}} It was first established to determine who would benefit from elective surgery for portal decompression. This scoring system uses multiple lab values including bilirubin, albumin, and INR. The presence of ascites and severity of encephalopathy is also included in the scoring. The classification system includes class A, B, or C.{{Cite web |title=Child-Pugh Score for Cirrhosis Mortality |url=https://www.mdcalc.com/child-pugh-score-cirrhosis-mortality |access-date=2022-03-23 |website=MDCalc}} Class A has a favorable prognosis while class C is at high risk of death.

The Child-Pugh score is a validated predictor of mortality after a major surgery. For example, Child class A patients have a 10% mortality rate and Child class B patients have a 30% mortality rate while Child class C patients have a 70–80% mortality rate after abdominal surgery. Elective surgery is usually reserved for those in Child class A patients. There is an increased risk for Child class B individuals and they may require medical optimization. Overall, it is not recommended for Child class C patients to undergo elective surgery.

In the past, the Child-Pugh classification was used to determine people who were candidates for a liver transplant. Child-Pugh class B is usually an indication for evaluation for transplant. However, there were many issues when applying this score to liver transplant eligibility. Thus, the MELD score was created.

The Model for End-Stage Liver Disease (MELD) score was later developed and approved in 2002.{{cite journal | vauthors = Singal AK, Kamath PS | title = Model for End-stage Liver Disease | journal = Journal of Clinical and Experimental Hepatology | volume = 3 | issue = 1 | pages = 50–60 | date = March 2013 | pmid = 25755471 | pmc = 3940492 | doi = 10.1016/j.jceh.2012.11.002 }} It was approved by the United Network for Organ Sharing (UNOS) as a way to determine the allocation of liver transplants to awaiting people in the United States.{{cite journal | vauthors = Peng Y, Qi X, Guo X | title = Child-Pugh Versus MELD Score for the Assessment of Prognosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis of Observational Studies | journal = Medicine | volume = 95 | issue = 8 | pages = e2877 | date = February 2016 | pmid = 26937922 | pmc = 4779019 | doi = 10.1097/MD.0000000000002877 }} It is also used as a validated survival predictor of cirrhosis, alcoholic hepatitis, acute liver failure, and acute hepatitis.{{Cite web |title=MELD Score (Model For End-Stage Liver Disease) (12 and older) |url=https://www.mdcalc.com/meld-score-model-end-stage-liver-disease-12-older |access-date=2022-03-24 |website=MDCalc}} The variables included bilirubin, INR, creatinine, and dialysis frequency. In 2016, sodium was added to the variables and the score is often referred to as MELD-Na.{{Cite web |title=MELDNa/MELD-Na Score for Liver Cirrhosis |url=https://www.mdcalc.com/meldna-meld-na-score-liver-cirrhosis |access-date=2022-03-24 |website=MDCalc}}

MELD-Plus is a further risk score to assess severity of chronic liver disease. It was developed in 2017 as a result of a collaboration between Massachusetts General Hospital and IBM.{{cite journal | vauthors = Kartoun U, Corey KE, Simon TG, Zheng H, Aggarwal R, Ng K, Shaw SY | title = The MELD-Plus: A generalizable prediction risk score in cirrhosis | journal = PLOS ONE | volume = 12 | issue = 10 | pages = e0186301 | date = 2017 | pmid = 29069090 | pmc = 5656314 | doi = 10.1371/journal.pone.0186301 | bibcode = 2017PLoSO..1286301K | doi-access = free }} Nine variables were identified as effective predictors for 90-day mortality after a discharge from a cirrhosis-related hospital admission. The variables include all Model for End-Stage Liver Disease (MELD)'s components, as well as sodium, albumin, total cholesterol, white blood cell count, age, and length of stay.

The hepatic venous pressure gradient (difference in venous pressure between incoming and outgoing blood to the liver) also determines the severity of cirrhosis, although it is hard to measure. A value of 16 mm or more means a greatly increased risk of death.{{cite journal | vauthors = Patch D, Armonis A, Sabin C, Christopoulou K, Greenslade L, McCormick A, Dick R, Burroughs AK | title = Single portal pressure measurement predicts survival in cirrhotic patients with recent bleeding | journal = Gut | volume = 44 | issue = 2 | pages = 264–269 | date = February 1999 | pmid = 9895388 | pmc = 1727391 | doi = 10.1136/gut.44.2.264 | url = http://gut.bmj.com/cgi/content/abstract/44/2/264 | url-status = live | archive-url = https://web.archive.org/web/20080528225834/http://gut.bmj.com/cgi/content/abstract/44/2/264 | archive-date = 2008-05-28 }}{{Unreliable medical source|reason=Primary study. Suggest to possibly remove the second sentence and keep the first if a better, modern, MEDRS-compliant source is found.|date=May 2022}}

Key prevention strategies for cirrhosis 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.{{cite web |url=https://www.lecturio.com/concepts/cirrhosis/ |title=Cirrhosis |website=The Lecturio Medical Concept Library |date=28 September 2020 |access-date=9 July 2021 |archive-date=9 July 2021 |archive-url=https://web.archive.org/web/20210709191841/https://www.lecturio.com/concepts/cirrhosis/ |url-status=live }}

Little is known about factors affecting cirrhosis risk and progression. However, many studies have provided increasing evidence for the protective effects of coffee consumption against the progression of liver disease. These effects are more noticeable in liver disease that is associated with alcohol use disorder. Coffee has antioxidant and antifibrotic effects. Caffeine may not be the important component; polyphenols may be more important. Drinking two or more cups of coffee a day is associated with improvements in the liver enzymes ALT, AST, and GGT. Even in those with liver disease, coffee consumption can lower fibrosis and cirrhosis.{{cite journal | vauthors = Wadhawan M, Anand AC | title = Coffee and Liver Disease | journal = Journal of Clinical and Experimental Hepatology | volume = 6 | issue = 1 | pages = 40–46 | date = March 2016 | pmid = 27194895 | pmc = 4862107 | doi = 10.1016/j.jceh.2016.02.003 }}

Generally, liver damage from cirrhosis cannot be reversed, but treatment can stop or delay further progression and reduce complications. A healthy diet is encouraged, as cirrhosis may be an energy-consuming process. A recommended diet consists of high-protein, high-fiber diet plus supplementation with branched-chain amino acids.{{cite journal | vauthors = Ruiz-Margáin A, Macías-Rodríguez RU, Ríos-Torres SL, Román-Calleja BM, Méndez-Guerrero O, Rodríguez-Córdova P, Torre A | title = Effect of a high-protein, high-fiber diet plus supplementation with branched-chain amino acids on the nutritional status of patients with cirrhosis | journal = Revista de Gastroenterologia de Mexico | volume = 83 | issue = 1 | pages = 9–15 | date = January 2018 | pmid = 28408059 | doi = 10.1016/j.rgmx.2017.02.005 | s2cid = 196487820 | doi-access = free }} Close follow-up is often necessary. Antibiotics are prescribed for infections, and various medications can help with itching. Laxatives, such as lactulose, decrease the risk of constipation. Carvedilol increases survival benefit for people with cirrhosis and portal hypertension.{{cite journal | vauthors = McDowell HR, Chuah CS, Tripathi D, Stanley AJ, Forrest EH, Hayes PC | title = Carvedilol is associated with improved survival in patients with cirrhosis: a long-term follow-up study | journal = Alimentary Pharmacology & Therapeutics | volume = 53 | issue = 4 | pages = 531–539 | date = February 2021 | pmid = 33296526 | doi = 10.1111/apt.16189 | hdl = 20.500.11820/83f830e0-832f-401e-bfe3-5576d368ea15 | s2cid = 228089776 | hdl-access = free }}

Diuretics in combination with low salt diet reduce fluid in body which helps reduce oedema.{{Cite web |title=Treatment of Cirrhosis |url=https://www.nhs.uk/conditions/cirrhosis/treatment/ |website=NHS|date=20 October 2017 }}

Alcoholic cirrhosis caused by alcohol use disorder 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.{{citation needed|date=September 2022}}

Cirrhosis caused by Wilson's disease is treated by removing the copper which builds up in organs. This is carried out using chelation therapy such as penicillamine. When the cause is an iron overload, iron is removed using a chelation agent such as deferoxamine or by bloodletting.{{citation needed|date=September 2022}}

As of 2021, there are recent studies studying drugs to prevent cirrhosis caused by non-alcoholic fatty liver disease (NAFLD or NASH). The drug semaglutide was shown to provide greater NASH resolution versus placebo. No improvement in fibrosis was observed.{{cite journal | vauthors = Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling AS, Harrison SA | title = A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis | journal = The New England Journal of Medicine | volume = 384 | issue = 12 | pages = 1113–1124 | date = March 2021 | pmid = 33185364 | doi = 10.1056/NEJMoa2028395 | s2cid = 226850568 | url = https://research.birmingham.ac.uk/portal/en/publications/a-placebocontrolled-trial-of-subcutaneous-semaglutide-in-nonalcoholic-steatohepatitis(cf786180-dab8-404d-98f3-68cd7de159ae).html | doi-access = free }} A combination of cilofexor/firsocostat was studied in people with bridging fibrosis and cirrhosis. It was observed to have led to improvements in NASH activity with a potential antifibrotic effect.{{cite journal | vauthors = Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G, Bhandari BR, Gunn N, Caldwell SH, Goodman Z, Wapinski I, Resnick M, Beck AH, Ding D, Jia C, Chuang JC, Huss RS, Chung C, Subramanian GM, Myers RP, Patel K, Borg BB, Ghalib R, Kabler H, Poulos J, Younes Z, Elkhashab M, Hassanein T, Iyer R, Ruane P, Shiffman ML, Strasser S, Wong VW, Alkhouri N | title = Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH | journal = Hepatology | volume = 73 | issue = 2 | pages = 625–643 | date = February 2021 | pmid = 33169409 | doi = 10.1002/hep.31622 | s2cid = 226295213 }} Lanifibranor is also shown to prevent worsening fibrosis.{{cite journal | vauthors = Francque SM, Bedossa P, Ratziu V, Anstee QM, Bugianesi E, Sanyal AJ, Loomba R, Harrison SA, Balabanska R, Mateva L, Lanthier N, Alkhouri N, Moreno C, Schattenberg JM, Stefanova-Petrova D, Vonghia L, Rouzier R, Guillaume M, Hodge A, Romero-Gómez M, Huot-Marchand P, Baudin M, Richard MP, Abitbol JL, Broqua P, Junien JL, Abdelmalek MF | title = A Randomized, Controlled Trial of the Pan-PPAR Agonist Lanifibranor in NASH | journal = The New England Journal of Medicine | volume = 385 | issue = 17 | pages = 1547–1558 | date = October 2021 | pmid = 34670042 | doi = 10.1056/NEJMoa2036205 | hdl = 1854/LU-8731444 | s2cid = 239051427 | url = https://eprints.ncl.ac.uk/277534 | doi-access = free | hdl-access = free }}

Regardless of the underlying cause of cirrhosis, consumption of alcohol and other potentially damaging substances is discouraged. There is no evidence that supports the avoidance or dose reduction of paracetamol in people with compensated cirrhosis; it is thus considered a safe analgesic for said individuals.{{cite journal | vauthors = Schweighardt AE, Juba KM | title = A Systematic Review of the Evidence Behind Use of Reduced Doses of Acetaminophen in Chronic Liver Disease | journal = Journal of Pain & Palliative Care Pharmacotherapy | volume = 32 | issue = 4 | pages = 226–239 | date = December 2018 | pmid = 31206302 | doi = 10.1080/15360288.2019.1611692 | s2cid = 190535151 | url = https://fisherpub.sjfc.edu/cgi/viewcontent.cgi?article=1215&context=pharmacy_facpub | url-access = subscription }}

Vaccination against hepatitis A and hepatitis B is recommended early in the course of illness due to decline in effectiveness of the vaccines with decompensation.{{cite journal|vauthors=Bajaj JS, Kamath PS, Reddy KR|title=The Evolving Challenge of Infections in Cirrhosis|journal=The New England Journal of Medicine|volume=384|issue=24|pages=2317–2330|doi=10.1056/NEJMra2021808|pmid=34133861|year=2021}}

Treating the cause of cirrhosis prevents further damage; for example, giving oral antivirals such as entecavir and tenofovir where cirrhosis is due to hepatitis B prevents progression of cirrhosis. Similarly, control of weight and diabetes prevents deterioration in cirrhosis due to non-alcoholic fatty liver disease.{{cite web |url= https://www.lecturio.com/concepts/nonalcoholic-fatty-liver-disease/| title= Nonalcoholic Fatty Liver Disease

|website=The Lecturio Medical Concept Library |access-date= 15 August 2021}}

People with cirrhosis or liver damage are often advised to avoid drugs that could further harm the liver. These include several drugs such as anti-depressants, certain antibiotics, and NSAIDs (like ibuprofen).{{cite journal | vauthors = Björnsson ES | title = Hepatotoxicity by Drugs: The Most Common Implicated Agents | journal = International Journal of Molecular Sciences | volume = 17 | issue = 2 | pages = 224 | date = February 2016 | pmid = 26861310 | pmc = 4783956 | doi = 10.3390/ijms17020224 | doi-access = free }} These agents are hepatotoxic as they are metabolized by the liver. If a medication that harms the liver is still recommended by a doctor, the dosage can be adjusted to aim for minimal stress on the liver.{{Citation needed|date=July 2023}}

According to a 2018 systematic review based on studies that implemented 8 to 14 week-long exercise programs, there is currently insufficient scientific evidence regarding either the beneficial or harmful effects of physical exercise in people with cirrhosis on all-cause mortality, morbidity (including both serious and non-serious adverse events), health-related quality of life, exercise capacity and anthropomorphic measures.{{cite journal|vauthors=Aamann L, Dam G, Rinnov AR, Vilstrup H, Gluud LL|date=December 2018|title=Physical exercise for people with cirrhosis|journal=The Cochrane Database of Systematic Reviews|volume=2018|issue=12|pages=CD012678|doi=10.1002/14651858.CD012678.pub2|pmc=6517144|pmid=30575956|collaboration=Cochrane Hepato-Biliary Group}} These conclusions were based on low to very low quality research, which imposes the need to develop further research with higher quality, especially to evaluate its effects on clinical outcomes.{{citation needed|date=September 2022}}

{{Main|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 risk factors in the recipient.{{cite web |url=http://www.emedicinehealth.com/liver_transplant/page11_em.htm |title=E-medicine liver transplant outlook and survival rates |publisher=Emedicinehealth.com |date=2009-06-09 |access-date=2009-09-06 |url-status=live |archive-url=https://web.archive.org/web/20090714145002/http://www.emedicinehealth.com/liver_transplant/page11_em.htm |archive-date=2009-07-14}} In the United States, the MELD score is used to prioritize patients for transplantation.{{cite journal | vauthors = Kamath PS, Kim WR | title = The model for end-stage liver disease (MELD) | journal = Hepatology | volume = 45 | issue = 3 | pages = 797–805 | date = March 2007 | pmid = 17326206 | doi = 10.1002/hep.21563 | s2cid = 10440305 | doi-access = free }} Transplantation necessitates the use of immune suppressants (ciclosporin or tacrolimus).

Manifestations of decompensation in cirrhosis include gastrointestinal bleeding, hepatic encephalopathy, jaundice or ascites. 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.

People with decompensated cirrhosis generally require admission to a hospital, with close monitoring of the fluid balance, mental status, and emphasis on adequate nutrition and medical treatment – often with diuretics, antibiotics, laxatives or enemas, thiamine and occasionally steroids, acetylcysteine and pentoxifylline.{{cite journal | vauthors = Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila FI, Soares-Weiser K, Uribe M | title = Antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD002907 | date = September 2010 | volume = 2010 | pmid = 20824832 | pmc = 7138054 | doi = 10.1002/14651858.CD002907.pub2 }} Administration of saline is avoided, as it would add to the already high total body sodium content that typically occurs in cirrhosis. Life expectancy without liver transplant is low, at most three years.

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.{{cite journal | vauthors = Ferrell B, Connor SR, Cordes A, Dahlin CM, Fine PG, Hutton N, Leenay M, Lentz J, Person JL, Meier DE, Zuroski K | title = The national agenda for quality palliative care: the National Consensus Project and the National Quality Forum | journal = Journal of Pain and Symptom Management | volume = 33 | issue = 6 | pages = 737–744 | date = June 2007 | pmid = 17531914 | doi = 10.1016/j.jpainsymman.2007.02.024 | doi-access = free }}

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.{{cite journal | vauthors = Sanchez W, Talwalkar JA | title = Palliative care for patients with end-stage liver disease ineligible for liver transplantation | journal = Gastroenterology Clinics of North America | volume = 35 | issue = 1 | pages = 201–219 | date = March 2006 | pmid = 16530121 | doi = 10.1016/j.gtc.2005.12.007 }} 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. Despite proven benefit, people with cirrhosis are rarely referred to palliative care.{{cite journal | vauthors = Poonja Z, Brisebois A, van Zanten SV, Tandon P, Meeberg G, Karvellas CJ | title = Patients with cirrhosis and denied liver transplants rarely receive adequate palliative care or appropriate management | journal = Clinical Gastroenterology and Hepatology | volume = 12 | issue = 4 | pages = 692–698 | date = April 2014 | pmid = 23978345 | doi = 10.1016/j.cgh.2013.08.027 }}

Cirrhosis is known to cause immune dysfunction in numerous ways. It impedes the immune system from working normally.

Cirrhosis can increase the risk of bleeding. The liver produces various proteins in the coagulation cascade (coagulation factors II, VII, IX, X, V, and VI). When damaged, the liver is impaired in its production of these proteins.{{cite journal | vauthors = O'Shea RS, Davitkov P, Ko CW, Rajasekhar A, Su GL, Sultan S, Allen AM, Falck-Ytter Y | title = AGA Clinical Practice Guideline on the Management of Coagulation Disorders in Patients With Cirrhosis | language = English | journal = Gastroenterology | volume = 161 | issue = 5 | pages = 1615–1627.e1 | date = November 2021 | pmid = 34579936 | doi = 10.1053/j.gastro.2021.08.015 | s2cid = 238202670 | doi-access = free }} This will ultimately increase bleeding as clotting factors are diminished. Clotting function is estimated by lab values, mainly platelet count, prothrombin time (PT), and international normalized ratio (INR).

The American Gastroenterological Association (AGA) provided recommendations in 2021 in regards to coagulopathy management of cirrhotic patients in certain scenarios.

• The AGA does not recommend for extensive pre-procedural testing, including repeated measurements of PT/INR or platelet count before patients with stable cirrhosis undergo common gastrointestinal procedures. Nor do they suggest the routine use of blood products, such as platelets, for bleeding prevention. Cirrhosis is stable when there are no changes in baseline abnormalities of coagulation lab values.
• For patients with stable cirrhosis and low platelet count undergoing common low-risk procedures, the AGA does not recommend the routine use of thrombopoietin receptor agonists for bleeding prevention.
• In hospitalized patients who meet standard guidelines for clot prevention, the AGA suggests standard prevention.
• The AGA does not recommend in routine screening for portal vein thrombosis. If there is a portal vein thrombosis, the AGA suggests treatment by anticoagulation.
• In the case of cirrhosis with atrial fibrillation, the AGA recommends using anticoagulation over no anticoagulation.

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.{{cite journal | vauthors = Moore KP, Aithal GP | title = Guidelines on the management of ascites in cirrhosis | journal = Gut | volume = 55 | issue = Suppl 6 | pages = vi1–v12 | date = October 2006 | pmid = 16966752 | pmc = 1860002 | doi = 10.1136/gut.2006.099580 }}

Where salt restriction and the use of diuretics are ineffective then paracentesis may be the preferred option.{{cite journal | vauthors = Piano S, Tonon M, Angeli P | title = Management of ascites and hepatorenal syndrome | journal = Hepatology International | volume = 12 | issue = Suppl 1 | pages = 122–134 | date = February 2018 | pmid = 28836115 | doi = 10.1007/s12072-017-9815-0 | s2cid = 3708859 }} This procedure requires the insertion of a plastic tube into the peritoneal cavity. Human serum albumin solution is usually given to prevent complications from the rapid volume reduction. In addition to being more rapid than diuretics, 4–5 liters of paracentesis is more successful in comparison to diuretic therapy.

For portal hypertension, nonselective beta blockers such as propranolol or nadolol are commonly used to lower blood pressure over the portal system. In severe complications from portal hypertension, transjugular intrahepatic portosystemic shunting (TIPS) is occasionally indicated to relieve pressure on the portal vein. As this shunting can worsen hepatic encephalopathy, it is reserved for those patients at low risk of encephalopathy. TIPS is generally regarded only as a bridge to liver transplantation{{cite journal | vauthors = Sellers CM, Nezami N, Schilsky ML, Kim HS | title = Transjugular intrahepatic portosystemic shunt as a bridge to liver transplant: Current state and future directions | journal = Transplantation Reviews | volume = 33 | issue = 2 | pages = 64–71 | date = April 2019 | pmid = 30477811 | doi = 10.1016/j.trre.2018.10.004 | s2cid = 53736623 }} or as a palliative measure.{{citation needed|date=January 2017}} Balloon-occluded retrograde transvenous obliteration can be used to treat gastric variceal bleeding.{{cite journal |vauthors=Lee EW, Shahrouki P, Alanis L, Ding P, Kee ST |date=June 2019 |title=Management Options for Gastric Variceal Hemorrhage |journal=JAMA Surgery |volume=154 |issue=6 |pages=540–548 |doi=10.1001/jamasurg.2019.0407 |pmid=30942880 |s2cid=93000660}}

Gastroscopy (endoscopic examination of the esophagus, stomach, and duodenum) is performed in cases of established cirrhosis. If esophageal varices are found, prophylactic local therapy may be applied such as sclerotherapy or banding, and beta blockers may be used.{{cite web |date=December 2006 |title=Gastroscopy – examination of oesophagus and stomach by endoscope |url=http://hcd2.bupa.co.uk/fact_sheets/html/Gastrointestinal.html |url-status=dead |archive-url=https://web.archive.org/web/20071006035730/http://hcd2.bupa.co.uk/fact_sheets/html/Gastrointestinal.html |archive-date=2007-10-06 |access-date=2007-10-07 |publisher=BUPA}}{{cite web |author=National Digestive Diseases Information Clearinghouse |author-link=National Digestive Diseases Information Clearinghouse |date=November 2004 |title=Upper Endoscopy |url=http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm |access-date=2007-10-07 |publisher=National Institutes of Health |archive-date=2007-10-24 |archive-url=https://web.archive.org/web/20071024122838/http://digestive.niddk.nih.gov/ddiseases/pubs/upperendoscopy/index.htm |url-status=dead }}{{cite web |title=What is Upper GI Endoscopy? |url=http://www.gastro.org/wmspage.cfm?parm1=859 |url-status=dead |archive-url=https://web.archive.org/web/20070928014913/http://www.gastro.org/wmspage.cfm?parm1=859 |archive-date=2007-09-28 |access-date=2007-10-07 |work=Patient Center -- Procedures |publisher=American Gastroenterological Association}}

Hepatic encephalopathy is a potential complication of cirrhosis. It may lead to functional neurological impairment ranging from mild confusion to coma. Hepatic encephalopathy is primarily caused by the accumulation of ammonia in the blood, which causes neurotoxicity when crossing the blood-brain barrier. Ammonia is normally metabolized by the liver; as cirrhosis causes both decreased liver function and increased portosystemic shunting (allowing blood to bypass the liver), systemic ammonia levels gradually rise and lead to encephalopathy.{{Cite journal |last=Lockwood |first=Alan H. |date=December 2004 |title=Blood Ammonia Levels and Hepatic Encephalopathy |url=http://link.springer.com/10.1023/B:MEBR.0000043980.74574.eb |journal=Metabolic Brain Disease |language=en |volume=19 |issue=3/4 |pages=345–349 |doi=10.1023/B:MEBR.0000043980.74574.eb |pmid=15554426 |s2cid=27884883 |issn=0885-7490|url-access=subscription }}

Most pharmaceutical approaches to treating hepatic encephalopathy focus on reducing ammonia levels.{{Cite web | vauthors = Ferenci P |date=Feb 2022 |title=Hepatic encephalopathy in adults: Treatment |url=https://www.uptodate.com/contents/hepatic-encephalopathy-in-adults-treatment |access-date=2022-03-22 |website=www.uptodate.com}} Per 2014 guidelines,{{Cite journal |last1=Vilstrup |first1=Hendrik |last2=Amodio |first2=Piero |last3=Bajaj |first3=Jasmohan |last4=Cordoba |first4=Juan |last5=Ferenci |first5=Peter |last6=Mullen |first6=Kevin D. |last7=Weissenborn |first7=Karin |last8=Wong |first8=Philip |date=2014-07-08 |title=Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study Of Liver Diseases and the European Association for the Study of the Liver: Vilstrup et al. |url=https://onlinelibrary.wiley.com/doi/10.1002/hep.27210 |journal=Hepatology |language=en |volume=60 |issue=2 |pages=715–735 |doi=10.1002/hep.27210|pmid=25042402 |hdl=11577/3147929 |hdl-access=free }} the first-line treatment involves the use of lactulose, a non-absorbable disaccharide which decreases the pH level of the colon when it is metabolized by intestinal bacteria. The lower colonic pH causes increased conversion of ammonia into ammonium, which is then excreted from the body.{{Cite journal |last=Elkington |first=S G |date=1970-12-01 |title=Lactulose. |journal=Gut |language=en |volume=11 |issue=12 |pages=1043–1048 |doi=10.1136/gut.11.12.1043 |issn=0017-5749 |pmc=1553161 |pmid=4929274}} Rifaximin, an antibiotic that inhibits the function of ammonia-producing bacteria in the gastrointestinal tract,{{Cite journal |last1=Adachi |first1=J. A. |last2=DuPont |first2=H. L. |date=2006-02-15 |title=Rifaximin: A Novel Nonabsorbed Rifamycin for Gastrointestinal Disorders |url=https://academic.oup.com/cid/article-lookup/doi/10.1086/499950 |journal=Clinical Infectious Diseases |language=en |volume=42 |issue=4 |pages=541–547 |doi=10.1086/499950 |pmid=16421799 |issn=1058-4838}} is recommended for use in combination with lactulose as prophylaxis against recurrent episodes of hepatic encephalopathy.{{Cite journal |last1=Bass |first1=Nathan M. |last2=Mullen |first2=Kevin D. |last3=Sanyal |first3=Arun |last4=Poordad |first4=Fred |last5=Neff |first5=Guy |last6=Leevy |first6=Carroll B. |last7=Sigal |first7=Samuel |last8=Sheikh |first8=Muhammad Y. |last9=Beavers |first9=Kimberly |last10=Frederick |first10=Todd |last11=Teperman |first11=Lewis |last12=Hillebrand |first12=Donald |last13=Huang |first13=Shirley |last14=Merchant |first14=Kunal |last15=Shaw |first15=Audrey |date=2010-03-25 |title=Rifaximin Treatment in Hepatic Encephalopathy |url=http://www.nejm.org/doi/abs/10.1056/NEJMoa0907893 |journal=New England Journal of Medicine |language=en |volume=362 |issue=12 |pages=1071–1081 |doi=10.1056/NEJMoa0907893 |pmid=20335583 |issn=0028-4793}}{{Cite journal |last1=Zacharias |first1=Harry D |last2=Kamel |first2=Fady |last3=Tan |first3=Jaclyn |last4=Kimer |first4=Nina |last5=Gluud |first5=Lise Lotte |last6=Morgan |first6=Marsha Y |date=2023-07-19 |editor-last=Cochrane Hepato-Biliary Group |title=Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis |journal=Cochrane Database of Systematic Reviews |language=en |volume=2023 |issue=7 |pages=CD011585 |doi=10.1002/14651858.CD011585.pub2 |pmc=10360160 |pmid=37467180}}

In addition to pharmacotherapy, providing proper hydration and nutritional support is also essential. Appropriate quantities of protein uptake is encouraged.{{cite journal |vauthors=Merli M, Berzigotti A, Zelber-Sagi S, Dasarathy S, Montagnese S, Genton L, Plauth M, Parés A |date=January 2019 |title=EASL Clinical Practice Guidelines on nutrition in chronic liver disease |journal=Journal of Hepatology |volume=70 |issue=1 |pages=172–193 |doi=10.1016/j.jhep.2018.06.024 |pmc=6657019 |pmid=30144956}} Several factors may precipitate hepatic encephalopathy, which include alcohol use, excess protein, gastrointestinal bleeding, infection, constipation, and vomiting/diarrhea. Drugs such as benzodiazepines, diuretics, or narcotics can also precipitate encephalopathic events. A low protein diet is recommended with gastrointestinal bleeding.

The severity of hepatic encephalopathy is determined by assessing the patient's mental status. This is generally a subjective assessment, although several attempts at creating criteria to help standardize this assessment have been published. One example is the West Haven criteria, reproduced below.

People with cirrhosis have a 40% lifetime risk of developing hepatic encephalopathy. The median survival after the development of hepatic encephalopathy is 0.9 years. Mild hepatic encephalopathy (also known as covert hepatic encephalopathy), in which symptoms are more subtle, such as impairments in executive function, poor sleep or balance impairment is also associated with a higher risk of hospitalization and death (18% in those with covert hepatic encephalopathy vs 3% in those with cirrhosis and no HE).

Hepatorenal syndrome is a serious complication of end-stage cirrhosis when kidney damage is also involved.{{cite journal | vauthors = Francoz C, Durand F, Kahn JA, Genyk YS, Nadim MK | title = Hepatorenal Syndrome | journal = Clinical Journal of the American Society of Nephrology | volume = 14 | issue = 5 | pages = 774–781 | date = May 2019 | pmid = 30996046 | pmc = 6500947 | doi = 10.2215/CJN.12451018 }} The annual risk of developing hepatorenal syndrome in those with cirrhosis is 8% and once the syndrome develops the median survival is 2 weeks.

Portal hypertensive gastropathy refers to changes in the mucosa of the stomach in people with portal hypertension, and is associated with cirrhosis severity.{{cite journal | vauthors = Kim MY, Choi H, Baik SK, Yea CJ, Won CS, Byun JW, Park SY, Kwon YH, Kim JW, Kim HS, Kwon SO, Kim YJ, Cha SH, Chang SJ | title = Portal hypertensive gastropathy: correlation with portal hypertension and prognosis in cirrhosis | journal = Digestive Diseases and Sciences | volume = 55 | issue = 12 | pages = 3561–3567 | date = December 2010 | pmid = 20407828 | doi = 10.1007/s10620-010-1221-6 | s2cid = 24332780 }}

Cirrhosis can cause immune system dysfunction, leading to infection. Signs and symptoms of infection may be nonspecific and are more difficult to recognize (for example, worsening encephalopathy but no fever).{{cite journal | vauthors = Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M | title = Immune dysfunction in cirrhosis | journal = World Journal of Gastroenterology | volume = 20 | issue = 10 | pages = 2564–2577 | date = March 2014 | pmid = 24627592 | pmc = 3949265 | doi = 10.3748/wjg.v20.i10.2564 | doi-access = free }} Moreover, infections in cirrhosis are major triggers for other complications (ascites, variceal bleeding, hepatic encephalopathy, organ failures, death).

Those with cirrhosis are at increased risk of infections as well as increased mortality from infections. This is due to a combination of factors including cirrhosis associated immune dysfunction, reduced gut barrier function, reduced bile flow, and changes in the gut microbiota, with an increase in pathobionts (native bacteria, that under certain conditions may cause infection).{{cite journal |last1=Bajaj |first1=Jasmohan S. |last2=Kamath |first2=Patrick S. |last3=Reddy |first3=K. Rajender |title=The Evolving Challenge of Infections in Cirrhosis |journal=New England Journal of Medicine |date=17 June 2021 |volume=384 |issue=24 |pages=2317–2330 |doi=10.1056/NEJMra2021808|pmid=34133861 }}

Cirrhosis associated immune dysfunction is caused by reduced complement component synthesis in the liver including C3, C4 and reduced total complement activity (CH50). The complement system is a part of the innate immune system and assists immune cells and antibodies in destroying pathogens. The liver produces compliment factors, but this may be reduced in cirrhosis, raising the risk of infections. Acute phase proteins (which help mount an immune response) and soluble pattern recognition receptors (which help immune cells to identify pathogens) are also reduced in those with cirrhosis, leading to further immune dysfunction. Cirrhosis is also associated with reduced Kupfer cell function, further increasing the risk for infections. Kupfer cells are resident macrophages in the liver which help to destroy pathogens.

Extrinsic factors may also increase the risk of infection in those with cirrhosis, including proton pump inhibitor use, alcohol use, frailty, antibiotic overuse, and hospitalizations or invasive procedures (which increase the risk of bacterial translocation to other areas of the body).

Infections that are common in those in the hospital with cirrhosis include spontaneous bacterial peritonitis (with a prevalence of 27% among hospitalized patients), urinary tract infections (22-29%), pneumonia (19%), spontaneous bacteremia (8-13%), skin and soft tissue infections (8-12%) and C. difficile colitis (2.4-4%).{{cite journal |last1=Piano |first1=Salvatore |last2=Singh |first2=Virendra |last3=Caraceni |first3=Paolo |title=Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide |journal=Gastroenterology |date=April 2019 |volume=156 |issue=5 |pages=1368–1380.e10 |doi=10.1053/j.gastro.2018.12.005|pmid=30552895 }} It is estimated that 3.5% of people with cirrhosis and ascites may have asymptomatic spontaneous bacterial peritonitis.{{cite journal |last1=Evans |first1=Luke |last2=Ray Kim |first2=W |last3=Poterucha |first3=John |last4=Kamath |first4=Patrick |title=Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites |journal=Hepatology |date=April 2003 |volume=37 |issue=4 |pages=897–901 |doi=10.1053/jhep.2003.50119|pmid=12668984 }}

The mortality rate for infections in those with cirrhosis is higher than that of the general population. In those with cirrhosis and severe infections with sepsis the mortality rate is greater than 50% and in those with septic shock, the mortality rate is 65%.

Hepatocellular carcinoma is the most common primary liver cancer, and the most common cause of death in people with cirrhosis.{{cite journal | vauthors = Forner A, Llovet JM, Bruix J | title = Hepatocellular carcinoma | journal = Lancet | volume = 379 | issue = 9822 | pages = 1245–1255 | date = March 2012 | pmid = 22353262 | doi = 10.1016/S0140-6736(11)61347-0 | s2cid = 24927898 }} Screening using an ultrasound with or without cancer markers such as alpha-fetoprotein can detect this cancer and is often carried out for early signs which has been shown to improve outcomes.{{cite journal | vauthors = Singal AG, Pillai A, Tiro J | title = Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis | journal = PLOS Medicine | volume = 11 | issue = 4 | pages = e1001624 | date = April 2014 | pmid = 24691105 | pmc = 3972088 | doi = 10.1371/journal.pmed.1001624 | doi-access = free }}

File:Cirrhosis of the liver world map-Deaths per million persons-WHO2012.svg

File:Cirrhosis of the liver world map - DALY - WHO2004.svg for cirrhosis of the liver per 100,000 inhabitants in 2004.{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=Nov 11, 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=2009-11-11}}{{Div col|small=yes|colwidth=10em}}

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Each year, approximately one million deaths are due to complications of cirrhosis, making cirrhosis the 11th most common cause of death globally.{{cite journal | vauthors = Asrani SK, Devarbhavi H, Eaton J, Kamath PS | title = Burden of liver diseases in the world | journal = Journal of Hepatology | volume = 70 | issue = 1 | pages = 151–171 | date = January 2019 | pmid = 30266282 | doi = 10.1016/j.jhep.2018.09.014 | s2cid = 52882095 }} 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.{{cite journal | vauthors = Anderson RN, Smith BL | title = Deaths: leading causes for 2001 | journal = National Vital Statistics Reports | volume = 52 | issue = 9 | pages = 1–85 | date = November 2003 | pmid = 14626726 }}

The cause of cirrhosis can vary; alcohol and non-alcoholic fatty liver disease are main causes in western and industrialized countries, whereas viral hepatitis is the predominant cause in low and middle-income countries. Cirrhosis is more common in men than in women.{{Cite book | vauthors = Tamparo C |title= Diseases of the Human Body | edition = 5th |publisher=F. A. Davis Company |year=2011 |isbn=978-0-8036-2505-1 |location=Philadelphia, PA |page=422}} The cost of cirrhosis in terms of human suffering, hospital costs, and lost productivity is high.

Globally, age-standardized disability-adjusted life year (DALY) rates have decreased from 1990 to 2017, with the values going from 656.4 years per 100,000 people to 510.7 years per 100,000 people.{{cite journal | vauthors = Sepanlou SG, Safiri S, Bisignano C, Ikuta KS, Merat S, Saberifiroozi M, etal | collaboration = GBD 2017 Cirrhosis Collaborators | title = The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 | journal = The Lancet. Gastroenterology & Hepatology | volume = 5 | issue = 3 | pages = 245–266 | date = March 2020 | pmid = 31981519 | pmc = 7026710 | doi = 10.1016/S2468-1253(19)30349-8 }} In males DALY rates have decreased from 903.1 years per 100,000 population in 1990, to 719.3 years per 100,000 population in 2017; in females the DALY rates have decreased from 415.5 years per 100,000 population in 1990, to 307.6 years per 100,000 population in 2017. However, globally the total number of DALYs have increased by 10.9 million from 1990 to 2017, reaching the value of 41.4 million DALYs.

The word "cirrhosis" is a neologism derived from {{langx|el|κίρρωσις}}; kirrhos {{lang|grc|κιρρός}}, meaning "yellowish, tawny" (the orange yellow colour of the diseased liver) and the suffix -osis, i.e. "condition" in medical terminology.{{LSJ|kirro/s|κιρρός|ref}}.{{OEtymD|cirrhosis}}{{OEtymD|-osis}} While the clinical entity was known before, René Laennec gave it this name in an 1819 paper.

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• Liver failure
• Liver regeneration

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{{reflist|colwidth=30em}}

{{Medical condition classification and resources

| DiseasesDB = 2729

| ICD10 = {{ICD10|K|70|3|k|70}}, {{ICD10|K|71|7|k|70}}, {{ICD10|K|74||k|70}}

| ICD9 = {{ICD9|571}}

| ICDO =

| OMIM =

| MedlinePlus = 000255

| eMedicineSubj = med

| eMedicineTopic = 3183

| eMedicine_mult = {{eMedicine2|radio|175}}

| MeshID = D008103

}}

• [https://web.archive.org/web/20111030040354/http://digestive.niddk.nih.gov/ddiseases/pubs/cirrhosis/ Cirrhosis of the Liver] at the National Digestive Diseases Information Clearinghouse (NDDIC). NIH Publication No. 04-1134, December 2003.
• {{cite web |url=https://medlineplus.gov/cirrhosis.html |publisher=U.S. National Library of Medicine |work=MedlinePlus |title=Cirrhosis}}

{{Alcohol and health}}

{{Gastroenterology}}

{{Organ failure}}

{{Authority control}}

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