- Clinical science
Cirrhosis is a condition caused by chronic damage to the liver, most commonly due to excessive alcohol consumption or hepatitis C infection. Other causes may include inflammatory or metabolic diseases, such as primary biliary cirrhosis or hemochromatosis. Cirrhosis is characterized by hepatic parenchymal necrosis and an inflammatory response to the underlying cause. Subsequent hepatic repair mechanisms lead to fibrosis and abnormal tissue architecture, which impair liver function. Patients may present with a range of symptoms, including jaundice, ascites, hepatosplenomegaly, and typical skin manifestations such as spider angioma or palmar erythema. Men may further display signs of feminization (e.g., gynecomastia, hypogonadism). In severe cases, accumulation of toxic metabolites or involvement of further organs can lead to complications such as hepatic encephalopathy or hepatorenal syndrome. Laboratory tests show signs of hepatocyte destruction (e.g., elevated liver enzymes, hyperbilirubinemia) or impaired hepatic synthetic function (e.g., prolonged prothrombin time, low albumin). Abdominal ultrasonography typically shows a shrunken, heterogeneous liver parenchyma with a nodular surface. Biopsy is the method of choice for confirming the diagnosis. However, it is usually only performed if previous testing was inconclusive. Management consists of treatment of the underlying disease (e.g., avoiding toxic substances, antiviral drugs), adequate calorie intake, and medication for treating complications (e.g., spironolactone for ascites). In cases of decompensated cirrhosis, interventional procedures (e.g., paracentesis to drain ascites) may be used to alleviate symptoms or bridge the time until liver transplantation is possible.
- Prevalence: approx. 0.27% in U.S. adults
- Sex: ♂ > ♀ (2:1)
- Responsible for approx. 1–2% of all deaths in the United States; most deaths occurring in the fifth to sixth decade of life
Epidemiological data refers to the US, unless otherwise specified.
- Metabolic disorders
- Cirrhosis of uncertain etiology despite adequate diagnostical efforts
|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|
- Although many factors contribute to the development of cirrhosis, cytokine‑mediated activation of stellate cells has been identified as a central element, as these cells promote fibrosis, which ultimately leads to cirrhosis.
- Hepatic inflammation → hepatocyte destruction which triggers repair mechanisms → excess formation of connective tissue (fibrosis); → loss of normal liver function (exocrine and metabolic)
- Inflammatory cytokines → hepatocyte destruction and stellate cell activation → excess collagen production; → loss of normal liver function (exocrine and metabolic)
Further pathophysiological mechanisms:
- Intrahepatic shunting between the portal vein and tributaries of the vena cava
- esophageal varices) (→
Impaired liver function
- Decreased synthesis of
- Further possible consequences
- Poor metabolism of medications → accumulation with increased risk of toxicity
- Increased insulin resistance (diabetes mellitus secondary to liver disease)
- Impaired hepatic metabolism of estrogen and androstenedione (which is then converted to estrogen by aromatase in adipose cells) →
- Limited enzymatic activation of vitamin D → secondary hyperparathyroidism
Nonspecific symptoms (patients are often initially asymptomatic)
- Fatigue, malaise, weight loss
- Fetor hepaticus
- Abdominal symptoms
- Skin changes
- Changes in the hepatic metabolization of sex hormones causes an imbalance in the estrogen‑androgen ratio, resulting in a marked increase of systemic estrogen levels. In men, increased estrogen causes feminization. As liver insufficiency worsens, plasma testosterone concentrations decrease.
- Signs of hepatocyte destruction
- Signs of impaired hepatic synthesis
- Macrocytic anemia due to vitamin deficiency (B12, folic acid)
- Microcytic anemia due to chronic blood loss
- Thrombocytopenia in hypersplenism
- Serum protein electrophoresis
Abdominal ultrasound should be performed first. Possible findings include:
- Liver form and structure
Liver size: initially enlarged, atrophies and shrinks with disease progression
- Hypertrophy of the caudate lobe
- Other possible findings
- CT scan
- Indication: Although biopsy is the gold standard for diagnosis, it is unnecessary in the light of clinical, laboratory, and ultrasound evidence. However, it can aid in identifying the etiology of the cirrhosis if prior testing was inconclusive.
Screening procedures and monitoring the disease course
HCC screening: abdominal ultrasound for patients with cirrhosis every 6 months and periodic monitoring of alpha-fetoprotein (AFP)
- Early diagnosis of hepatocellular carcinoma is possible.
Before taking a biopsy, check the patient's coagulation status as the risk of bleeding may be increased!
|Size of the regenerative nodules||Occurrence|
|Macronodular||> 3 mm|
|Both||1–3 mm and > 3 mm|| |
- Treatment of the primary condition
- Avoidance of hepatotoxic substances (e.g., alcohol, medication)
- Routine vaccinations; (influenza, pneumococcal disease, hepatitis A/B, tetanus )
- Balanced diet with adequate calorie intake, no protein restriction
Medication (for treatment of complications see respective section)
- Non‑selective 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
- In cases of coagulation factor deficiency (possibly combined with thrombocytopenia): leads to coagulation disturbances and bleeding diathesis
- Interventional procedures
- Surgery: A liver transplant is the only curative option in advanced liver disease.
The following complications are covered in separate sections below or in other separate cards:
- Definition: worsening of liver function in cirrhosis characterized by the presence of jaundice, ascites, variceal hemorrhage, or hepatic encephalopathy
- Hematologic manifestations
Complications caused by portal hypertension
- and subsequent
Metabolic complications or associated organ impairment
- Hepatopulmonary syndrome
We list the most important complications. The selection is not exhaustive.
Definition: Hepatic encephalopathy (HE) is defined as fluctuations in mental status and cognitive function in the presence of severe liver disease. Hepatic dysfunction results in inadequate elimination of metabolic products with subsequent accumulation of neurotoxic metabolites (like ammonia).
- Disturbances of consciousness, ranging from mild confusion to coma
- Multiple neurological and psychiatric disturbances like:
- General measures
- Avoidance of trigger substances (e.g., hepatotoxic medication, alcohol)
- Treatment of further complications which might aggravate HE (see “Triggers” above)
Lactulose: synthetic disaccharide laxative
- First-line treatment for HE
- Improves HE by decreasing absorption of ammonia in the bowel: lactulose is converted to lactic acid by intestinal 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 
- General measures
- Definition: deterioration of kidney function in patients with advanced liver disease. The condition is caused by renal vasoconstriction resulting in hypoperfusion of the kidneys.
- Triggers: loss of volume
- General measures: improvement of liver function if possible (e.g., cessation of alcohol use)
- Pharmacotherapy: combination of midodrine, octreotide, and albumin
- Definition: complete or partial closure of the portal vein
- Complication of cirrhosis or chronic liver disease
- Myeloproliferative syndrome
- Thrombophilia (e.g., antiphospholipid syndrome) or general risk factors of phlebothrombosis.
- Chronic mesenteric venous thrombosis
- Local complications of intra-abdominal malignancy (e.g., pancreatic carcinoma) or inflammation (e.g., liver abscess)
- Symptoms: The condition can take many different courses, depending on the extent of thrombosis and the speed of manifestation.
- Color duplex sonography
- CT or MRI of the abdomen with contrast agent
- Treatment with anticoagulants for 3–6 months results in fibrinolysis and recanalization (complete recanalization occurs in about 50% of cases).
- Treatment of complications (such as stopping acute bleeding from esophageal varices)
- Transhepatic thrombolysis with tissue plasminogen activator. Recommended in acute portal vein thrombosis
- Definition: a condition characterized by hypoxemia, intrapulmonary vasodilatation, and portal hypertension in the presence of cirrhosis
- Patients may also manifest with platypnea or orthodeoxia
- Definition: portopulmonary hypertension is a form of pulmonary arterial hypertension (PAH), which is associated with portal hypertension. It is a well recognized complication of chronic liver disease.
- Pathophysiology: the cause remains unknown; vasoactive substances bypass hepatic metabolism and reach the pulmonary circulation
- Clinical features: same symptoms as
- Diagnostic: echocardiography; right heart catheter for specific diagnostics
- Therapy: supportive measures, no causal therapy
- Further pulmonary complications in cirrhosis