Cirrhosis is a condition caused by chronic damage to the liver, most commonly due to excessive alcohol consumption, nonalcoholic fatty liver disease, 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 can present with a range of symptoms, including ascites, hepatosplenomegaly; and skin manifestations of cirrhosis, such as jaundice, spider angioma, and/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 damage (e.g., elevated liver enzymes, hyperbilirubinemia) or impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal ultrasonography typically shows shrunken, heterogeneous liver parenchyma with a nodular surface. A biopsy is the method of choice for confirming the diagnosis. However, it is usually only performed if previous diagnostic modalities were inconclusive. Management consists of treatment of the underlying disease (e.g., avoiding toxic substances, antiviral drugs), adequate caloric 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.
- Prevalence: approx. 0.27% in US adults 
- Sex: ♂ > ♀ (2:1) 
- Responsible for approx. 1–2% of all deaths in the US (12th leading cause of death)
- Most deaths occur in the fifth to sixth decade of life.
Epidemiological data refers to the US, unless otherwise specified.
- Long-standing alcohol use disorder (one of the two most common causes of chronic liver disease in the US)
- Medications; (e.g., acetaminophen, amiodarone, chemotherapy drugs such as methotrexate)
- Ingestion of (produced by Aspergillus) 
- Industrial chemicals such as tetrachloromethane and various pesticides
- Inflammation (hepatitis)
- Metabolic disorders
Hepatic vein congestion or vascular anomalies
- (congestive hepatopathy)
- Cryptogenic cirrhosis: cirrhosis of uncertain etiology despite adequate diagnostical efforts
Cryptogenic cirrhosis is a diagnosis of exclusion and should only be considered after a complete patient evaluation has ruled out all other possible causes of cirrhosis.
- Cirrhosis is characterized by irreversible diffuse fibrosis of the liver (the final common pathway for chronic liver diseases).
- Pathogenesis is multifactorial.
The following three mechanisms have been described for all types of liver cirrhosis: 
- Degeneration and necrosis of hepatocytes
Fibrotic tissue and regenerative nodules replace the liver parenchyma
- Hepatocyte destruction triggers repair mechanisms → excess formation of connective tissue (fibrosis)
- Excessive connective tissue in periportal zone and centrilobular zone → regenerative nodules and fibrous septa → compression of hepatic sinusoids and venules → ↑ portal vein hydrostatic pressure → intrasinusoidal hypertension → ↓ functional sinusoids
- Loss of liver function: sinusoidal capillarization → loss of fenestration and scar tissue formation→ impaired substrate exchange →; loss of normal liver function (exocrine and metabolic)
- Nonspecific features
- Telangiectasia: most commonly spider angiomata
- Caput medusae: paraumbilical dilation of subcutaneous veins
- Palmar erythema (plantar erythema also possible) 
- Petechiae and purpura
- Generally dry and atrophic
- White nails with ground-glass opacity (also known as “Terry nails”)
- Nail clubbing
- Lacquered lips, smooth red tongue
- Abdominal features
- Changes in the hepatic metabolization of sex hormones cause an imbalance in the estrogen-androgen ratio, resulting in a marked increase in systemic estrogen levels.
- In men, increased estrogen levels cause feminization.
- In women, a massive increase in estrogen can cause amenorrhea.
- Hyperestrogenism 
- Specific clinical features due to rare etiologies
Laboratory tests 
Parameters of hepatocyte damage
↑ Transaminases (AST, ALT)
- ALT > AST: present in most liver diseases
- AST > ALT: indicative of alcoholic liver disease
- Initially normal/↑ bilirubin
- ↑ Gamma‑glutamyl transpeptidase (GGT)
- ↑ Alkaline phosphatase
- ↑ Glutamate dehydrogenase (GDH)
- ↑ Ammonia
- ↑ Transaminases (AST, ALT)
Parameters of impaired hepatic synthesis
- ↑ Prothrombin time (↑ INR): due to decreased production of coagulation factors
- ↓ Total protein (↓ albumin)
- ↓ Plasma cholinesterase (CHE) 
- Other (rarer) tests
Other laboratory tests
- Hepatitis: anti‑HBs, anti‑HBc, HBsAg, and anti‑HCV
- α1 antitrypsin deficiency: serum α1-antitrypsin
- Hemochromatosis: serum iron, ferritin, transferrin saturation
- Wilson disease: serum and urine copper, serum ceruloplasmin
- Autoimmune hepatitis: hypergammaglobulinemia in the serum protein electrophoresis, AMA, ASMA, Anti-LKM-1 antibody
- PBC: positive anti-mitochondrial antibodies (AMA or AMA-M2), ↑ alkaline phosphatase, ↑ bilirubin
- PSC: cholestasis parameters (↑GGT, ↑ alkaline phosphatase, and ↑ bilirubin) ↑ pANCA
- Best initial imaging study
- Liver form and structure findings
Liver size findings
- Initially enlarged
- Atrophies and shrinks with disease progression
- Other possible findings
- CT scan
- Transient elastography
- Execution: usually ultrasound‑guided transcutaneous approach (easily performed, but may have limited diagnostic value if only a small tissue sample can be taken)
- Indications: Biopsy is the gold standard for diagnosis of cirrhosis. However, it should only be considered if clinical, laboratory, and ultrasound evidence is unclear.
- Alternative methods
Before taking a biopsy, check the patient's coagulation status as the risk of bleeding may be increased.
Monitoring the disease course
- Fibrosis (fibrous septa)
- Replacement of normal liver tissue with collagenous regenerative nodules (histological staging is based on the size of the regenerative nodules) 
- Abnormal cell activation with infiltration of inflammatory cells
- Loss of physiological vessel architecture (central vein disappearance)
|Size of the regenerative nodules||Occurrence|
|Both|| || |
- See “,” “,” and “ for specific pathological findings related to these conditions.
General approach 
- Provide treatment for the underlying condition (e.g., treat HCV with antiviral drugs and reduce hepatotoxic influences).
- Prevent, recognize, and treat possible complications.
- Avoidance of hepatotoxic substances (e.g., alcohol, medications such as NSAIDs)
- Routine vaccinations: pneumococcal vaccine (PPSV23), hepatitis A vaccine, hepatitis B vaccine, influenza vaccine, tetanus vaccine
- Balanced diet with adequate calorie intake, no protein restriction
- Nonselective beta blockers (e.g., propranolol) to lower portal pressure and prevent variceal bleeding (see “Treatment” of “”).
- Spironolactone and furosemide to manage ascites and edema in patients with hypoalbuminemia
- For the treatment of specific complications related to cirrhosis, see the conditions listed in “Complications” below.
Surgical/Interventional procedures 
- Paracentesis: a method used to decompress abdomen due to ascites
- Transjugular intrahepatic portosystemic shunt ( ): a method used to lower portal pressure and manage complications
- Surgery: A liver transplant is the only curative option in patients with decompensated cirrhosis.
- Decompensated cirrhosis: worsening of liver function in cirrhosis characterized by the presence of jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy
Major complications 
Complications caused by
- and subsequent
- Hematologic complications:
Metabolic complications or associated organ impairment
- Tumors: HCC) (
- Complications caused by
- Other complications
We list the most important complications. The selection is not exhaustive.
- Fluctuations in mental status and cognitive function in the presence of severe liver disease (e.g., cirrhosis)
Cirrhosis → ↓ hepatic metabolism and portosystemic shunt → accumulation of neurotoxic metabolites, especially ammonia (NH3) → excess glutamine and swelling produced by astrocytes → cerebral edema and ↑ intracranial pressure → neurological deterioration
- Hypokalemia → shift of K+ ions out of the cells → shift of H+ ions into the cells to maintain electroneutrality → intracellular acidosis → tubular cells produce more ammonia → neurological deterioration
- Metabolic alkalosis → decreased H+ ion availability → decreased conversion of ammonia to ammonium (NH4+)→ increased levels of ammonia → diffuses freely through the blood-brain barrier → neurological deterioration
Precipitant factors 
- Increased absorption or production of ammonia
- Decreased metabolism and clearance of ammonia
Symptoms are usually reversible.
- Fatigue, lethargy, apathy
- Altered , ranging from mild confusion to stupor or coma
- Memory loss
- Impaired sleeping patterns
- Multiple neurological and psychiatric disturbances
- Socially aberrant behavior (e.g., urinating/defecating in public, shouting at strangers)
- Slurred speech
- Muscle rigidity
- Based on the patient's medical history and clinical presentation
Assessment of mental status
- Number connection test: test in which patients are timed while connecting numbers in order that are randomly distributed over a piece of paper (in hepatic encephalopathy it is completed slower than the age-normalized standard or not completed)
- Psychometry‑based diagnostic method (e.g., Mini-Mental State Examination) 
- Laboratory studies: elevated serum ammonia levels
- Avoidance and correction of precipitating factors (e.g., hepatotoxic medication, alcohol, _Definitions"#Z2c4b7b192fbfa8d2679ddc134ed0e9c5" data-lxid="Ig0Y92">hypovolemia, electrolyte disturbances)
- Treatment of further complications that might aggravate the encephalopathy
Lactulose: a synthetic disaccharide laxative
- First-line treatment for hepatic encephalopathy
- Improves hepatic encephalopathy by decreasing absorption of ammonia in the bowel: lactulose is converted to lactic acid by intestinal flora → acidification in the gut leads to conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentration
- Rifaximin: a broad-spectrum, nonabsorbable oral antibiotic
- Lactulose: a synthetic disaccharide laxative
- The exact pathomechanisms are not completely understood.
- Cirrhosis/portal hypertension → ↑ splanchnic vasodilators (e.g., nitric oxide) → ↓ arterial blood flow → activation of RAAS → renal vasoconstriction → ↓ GFR
Generally attributed to the loss of volume
- Drainage of large volume ascites
- Gastrointestinal bleeding
- Forced diuresis
- Excess use of laxatives (lactulose)
- Post TIPS procedure
Clinical features 
- For clinical features associated with advanced liver disease, see “” in “Complications.”
- Ranging from oliguria up to anuria with progressive kidney failure
- Hypotension and wide pulse pressure
Hepatorenal syndrome is a clinical diagnosis based on reduced glomerular filtration rate in patients with cirrhosis and no other causes for renal failure (e.g., shock) or no detection of renal pathologies on ultrasound.
Diagnostic criteria 
- Serum creatinine ≥ 0.3 mg/dL within 48 hours or ≥ 50% from baseline
- Lack of improvement in renal function after volume expansion with albumin and at least 48 hours without diuretics
- Urinary output ≤ 0.5 ml/kg
- Decreased urine sodium levels (< 10 mmol/L)
- No proteinuria > 500 mg/dL, no microhematuria, no acute pathological findings in the kidney ultrasound
- No exposure to nephrotoxic drugs
- Absence of shock
- General measures: improvement of liver function if possible (e.g., cessation of alcohol use, avoid nephrotoxic drugs)
- Surgical/interventional procedures
- Possibly caused by an imbalance of coagulation factors in patients with impaired hepatic synthetic function
- The closure of portal vein flow → ↓ liver blood flow → vasodilation of the hepatic artery and development of collateral hepatic veins in an attempt to maintain liver perfusion
- Thrombotic closure of the splenic and superior mesenteric veins may extend to the portal vein → portal hypertension
- Cirrhosis or chronic liver disease
- Local complications of intraabdominal malignancy (e.g., HCC, pancreatic carcinoma) or inflammation (e.g., liver abscess, pancreatitis, cholangitis)
- Thrombophilia (e.g., antiphospholipid syndrome, factor V Leiden) or general risk factors of phlebothrombosis
- Myeloproliferative disorder
- Following TIPS procedure
- Chronic mesenteric venous thrombosis
Depend on the extent of thrombosis and the speed of manifestation
- Acute portal vein thrombosis
- Chronic portal vein thrombosis
- Ultrasound findings
Color duplex ultrasound
- Confirmatory test
- Shows decreased flow velocity or complete halt of flow
- CT or MRI of the abdomen with contrast agent
The goal is to prevent precipitant factors, thrombosis extension, and achieve portal vein recanalization. There are no generalized management recommendations for cirrhotic patients with portal vein thrombosis.
- Given for 3–6 months
- Complete recanalization occurs in about 50% of patients.
Surgical/Interventional procedures 
Transjugular intrahepatic portosystemic shunt (TIPS)
- Can be considered for individuals with cirrhosis and chronic PVT
- Cases of uncontrollable variceal bleeding in individuals with cirrhosis
- Percutaneous transhepatic thrombolysis with tissue plasminogen activator (tPA): individuals with cirrhosis and acute portal vein thrombosis
- Liver transplant: depends on the extent of thrombosis
- Transjugular intrahepatic portosystemic shunt (TIPS)
Hepatopulmonary syndrome 
- A condition characterized by hypoxemia, intrapulmonary vasodilatation, and portal hypertension in the presence of cirrhosis
- Not completely understood
- Portal hypertension and liver damage → translocation of bacterial endotoxins → changes in the production of cytokines and pulmonary vasodilators → ↑ nitric oxide in the lung vessels → pulmonary vasodilation → hepatopulmonary syndrome
- Medical history: diagnosis of advanced liver disease
- Arterial blood gas analysis: alveolar-arterial gradient (AaO2) ≥ 15 mmHg or ≥ 20 mmHg in patients > 64 years old while in a seating position
- Supportive measures: Long‑term treatment with oxygen is recommended.
- Surgical procedure: liver transplant
Portopulmonary hypertension 
- Not completely understood
- High cardiac output in advanced liver disease → wall shear stress in pulmonary vasculature → ↑ vasoactive and angiogenic substances (e.g., endothelin-1) → hypertrophy of smooth muscle cells and fibroblasts, fibrosis of intimal sheath, and microaneurysms of pulmonary arterioles
- Often asymptomatic
- Clinical findings are the same as in
- Medical history: portal hypertension or cirrhosis
- Diagnostic criteria
- Supportive measures: to alleviate symptoms
- Pharmacotherapy: Epoprostenol, bosentan, or sildenafil have insufficient data to make generalized recommendations.
- Surgical procedure: liver transplantation
Other pulmonary complications in cirrhosis
- immunosuppression : due to
- ascites : diaphragm is elevated due to massive
- Lung emphysema: in α1-antitrypsin deficiency
Hepatic hydrothorax: mostly one‑sided pleural effusions (70% right, 18% left) with transudate characteristics 
- Pathophysiology: caused by increased permeability of the diaphragm on account of microperforations, increased lymphatic leakage, and hypoalbuminemia
- Clinical findings: dyspnea (at rest)
- Pleural tap for symptomatic relief
- In cases of recurring fluid accumulation, continuous drainage should be considered.
Liver transplantation should be considered when medical treatment of cirrhosis has failed. Risk stratification for liver transplant is done by using the Model for End-Stage Liver Disease ( ) and Child-Pugh score systems. 
- A prognostic grading scale to assess the severity of cirrhosis, on the basis of specific laboratory markers (e.g., bilirubin, albumin, prothrombin time), as well as ascites and encephalopathy
|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|
|Child-Pugh class A: 5–6 points; Child-Pugh class B: 7–9 points; Child-Pugh class C: 10–15 points|
- An additional model used to predict prognosis in patients with cirrhosis, in terms of three-month mortality
- Primarily used to prioritize patients needing liver transplantation
- Patients are given a score from 1–40 based on serum bilirubin, INR, and creatinine levels.
- The higher the score, the worse the prognosis.