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. Other causes include inflammatory or metabolic diseases, such as primary biliary cirrhosis and 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 also display signs of feminization (e.g., gynecomastia, hypogonadism). In severe cases, the accumulation of toxic metabolites or involvement of additional organs can lead to complications such as hepatic encephalopathy and hepatorenal syndrome (HRS). Laboratory studies show signs of hepatocyte damage (e.g., elevated liver enzymes, hyperbilirubinemia) and/or impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal ultrasound 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 the results from other diagnostic modalities are inconclusive. Management consists of treatment of the underlying disease (e.g., avoidance of toxic substances, antiviral drugs), adequate calorie intake, and medication for treating complications (e.g., spironolactone for ascites). In cases of decompensated cirrhosis, interventional procedures may be used to alleviate symptoms (e.g., paracentesis to drain ascites) or as a bridge until liver transplantation is possible.
- 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 aflatoxin (produced by Aspergillus) 
- Industrial chemicals such as tetrachloromethane and various pesticides
- Metabolic disorders
- Hepatic vein congestion or vascular anomalies
- 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)
Patients with cirrhosis can be asymptomatic (compensated cirrhosis). Disease progression leads to fatigue, weight loss, abdominal distention, and spider angiomata followed by decompensated cirrhosis, manifesting with bleeding varices, ascites, encephalopathy, and jaundice.
- Telangiectasia: most commonly spider angiomata (a central red arteriole with numerous, thin arterial extensions, commonly manifesting on light, sun-exposed skin and the trunk)
- Caput medusae
- Palmar erythema (plantar erythema also possible) 
- Nail clubbing
- Petechiae and purpura
- Generally dry and atrophic skin
- White nails with ground-glass opacity (also known as “Terry nails”)
- Lacquered lips, smooth red tongue
- 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.
- Fetor hepaticus: bad breath with a characteristic sweet, pungent smell caused by an accumulation of dimethyl sulfide
- Dupuytren contracture
- Peripheral edema 
- See also “Clinical features” in “ .”
Specific clinical features due to rare causes
General principles 
- Diagnosis is typically based on a combination of typical clinical features, laboratory findings, and features on imaging but liver biopsy is the gold standard.
- Initial evaluation:
- Additional evaluation (e.g., biopsy) may be needed to stage fibrosis or if the etiology remains unclear
- Periodically evaluate for complications (e.g., HCC, esophageal varices).
Routine laboratory studies 
Transaminases: ↑ ALT and AST
- ALT > AST: present in most liver diseases (e.g., NAFLD, viral hepatitis)
- AST > ALT: indicative of alcoholic liver disease and/or cirrhosis of any etiology
- Massive AST and/or ALT elevation (> 15 times ULN): Consider differential diagnoses (e.g., acetaminophen toxicity, acute viral hepatitis, autoimmune hepatitis).
- ↑ Bilirubin (may be normal initially)
- ↑ ALP
- ↑ Gamma‑glutamyl transferase (GGT)
- Transaminases: ↑ ALT and AST
- Coagulation studies: ↑ prothrombin time (↑ INR) because of decreased production of coagulation factors
Some CBC abnormalities are due to the combination of increased hepatic and splenic sequestration of thrombocytes (portal hypertension leads to splenomegaly with ) and decreased production of hematopoietic factors by the liver.
Additional laboratory studies 
- Viral hepatitis: especially in patients with risk factors
- NASH: fasting lipid levels and HbA1c
- Hemochromatosis: serum iron, ferritin, transferrin saturation
- Alcoholic liver disease: assess for alcohol use disorder; consider measuring alcohol biomarkers.
- Autoimmune hepatitis: total IgG or serum electrophoresis (showing hypergammaglobulinemia), ANA, ASMA, anti-LKM-1 antibody, anti-soluble liver antigen antibody
- Alpha-1 antitrypsin deficiency: alpha-1 antitrypsin level and phenotype
- Wilson disease: serum ceruloplasmin, serum total and free copper, urinary copper
- Primary biliary cholangitis: antimitochondrial antibodies (AMA or AMA-M2), ALP, bilirubin
- Primary sclerosing cholangitis: cholestasis parameters (GGT, ALP, and bilirubin), pANCA, IgG
- Other tests 
Abdominal ultrasound with Doppler 
- Suspected cirrhosis: best initial test
- Established cirrhosis: for HCC screening and detecting complications
- Liver form and structure
- Liver size
- Other possible findings
CT abdomen 
- Indication: patients in whom adequate assessment with ultrasound is not possible (e.g., because of obesity)
- Findings: similar to those on ultrasound
Liver biopsy 
- Findings: See “Pathology.”
Screening for complications
- Screening for esophageal varices: EGD at time of diagnosis and every 1–3 years depending on the presence and size of the varices on initial screening 
- HCC screening: abdominal ultrasound every 6 months 
These biomarker-based tools can be used as an adjunct to confirm and stage cirrhosis of certain etiologies.
- AST-to-platelet ratio index (APRI)
- Fibrosis-4 score
- NAFLD fibrosis score
Liver elastography 
- Definition: a technique that measures liver stiffness to help determine the degree of fibrosis
- Indication: diagnosis and staging of liver fibrosis and cirrhosis
- Transient elastography (most common): uses a device (FibroScan®) that only performs elastography; no direct visualization of the liver
- Acoustic radiation force impulse: It is integrated into a conventional ultrasound system, enabling simultaneous elastography and visualization of the liver. 
- Other: magnetic resonance elastography, strain elastography
Model for end-stage liver disease score (MELD score) 
- Used to predict the three-month mortality rate of patients with cirrhosis
- Primarily used to prioritize patients for liver transplantation 
- Patients are given a score from 6 to 40 based on serum bilirubin, INR, and creatinine levels.
- Patients with high scores have the worst prognosis without intervention and should therefore be prioritized for transplantation (if appropriate)
Child-Pugh score 
- A prognostic grading scale that assesses survival rate and predicts the likelihood of developing complications based on bilirubin and albumin levels, prothrombin time, and the presence of ascites and encephalopathy
- Can be used as a prognostic scoring system 
- Child‑Pugh class A: one-year survival rate of ∼ 100%
- Child‑Pugh class B: one-year survival rate of ∼ 80%
- Child‑Pugh class C: one-year survival rate of ∼ 45%
|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|
General principles 
Patients with cirrhosis are typically managed in consultation with specialists.
- Treat the underlying condition (e.g., antivirals for HCV); see “Etiology.”
- Screen for, recognize, and treat complications and decompensations (see “Complications of cirrhosis”).
- Provide supportive care to:
- Conduct regular staging of cirrhosis (see “Staging of cirrhosis”)
- Consider workup for liver transplantation, depending on stage and etiology.
Supportive care 
- Avoid hepatotoxic substances.
- Nonselective beta blockers (e.g., propranolol) may be indicated for prophylaxis of esophageal varices and to prevent variceal bleeding
- Routine vaccinations: pneumococcal (PPSV23), hepatitis A, hepatitis B, influenza, SARS-CoV-2, and tetanus 
- Avoidance of raw seafood and unpasteurized dairy 
- Prophylactic antibiotics (e.g., after previous spontaneous bacterial peritonitis or GI bleeding)
- Nutrition: Aim for a balanced diet with adequate calorie intake. 
Liver transplant 
- 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.
|Overview of common complications of cirrhosis |
|Portal hypertension complications|
|Hemostatic abnormalities (coagulopathy)|
We list the most important complications. The selection is not exhaustive.
- Definition: the development of ascites, hepatic encephalopathy, or GI bleeding in patients with cirrhosis 
- Onset: can be triggered by an acute event (e.g., bleeding, sepsis) or develop gradually (e.g., ascites, encephalopathy) 
- Common precipitating factors
- Diagnostics: to establish the cause of decompensation
Acute management: See “Management of acute liver failure.” 
- Gastroenterology consult
- Treat the underlying cause and complications (if applicable).
- Prognosis: In patients with decompensated cirrhosis, survival rates are usually poor unless liver transplantation is performed.
Pulmonary complications 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
Clinical features 
- Diagnostic criteria: All criteria must be fulfilled.
- Pulse oximetry: (screening test): Hypoxemia
- Supportive management
- Definitive treatment: liver transplantation 
Portopulmonary hypertension (POPH) 
- 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
Clinical features 
- May be asymptomatic
- Features of right heart failure
Risk factors 
- Female sex
- Autoimmune liver disease
- Transthoracic Doppler echocardiography (initial): Typical findings include right ventricular hypertrophy or dysfunction, and increased right ventricular systolic pressure.
- Right heart catheterization (gold standard) 
- Diagnostic criteria: All criteria must be fulfilled.
- Definitive treatment: liver transplantation
Hepatic hydrothorax 
- Definition: pleural effusions (typically one-sided; 70% right, 18% left) with transudate characteristics in the absence of any other cardiac, pulmonary, or pleural disease 
- Pathophysiology: increased permeability of the diaphragm (small defects, increased abdominal pressure)
- Clinical presentation
- Diagnosis: Thoracocentesis shows transudate.
Other pulmonary complications
Special patient groups
Liver cirrhosis in pregnancy 
- Worsening of liver cirrhosis; pregnancy in individuals with advanced disease is associated with increased risk of:
- Increased risk of pregnancy-related complications, including:
- Fetal complications: associated with increased rates of newborn asphyxia and small size for gestational age