• Clinical science

Cirrhosis

Summary

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

Epidemiology

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

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

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

Classification

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

References:[8][9]

Pathophysiology

References:[10]

Clinical features

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

Diagnostics

Laboratory tests

Imaging studies

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

Biopsy

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

Screening procedures and monitoring the disease course

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

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

Pathology

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

Treatment

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

Complications

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

Decompensated cirrhosis

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

References:[8][20]

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

Hepatic encephalopathy

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

  • Triggers
  • Clinical manifestations
    • Disturbances of consciousness, ranging from mild confusion to coma
    • Multiple neurological and psychiatric disturbances like:
      • Asterixis
      • Fatigue, lethargy, apathy
      • Memory loss
      • Impaired sleeping patterns
      • Irritability
      • Disoriented, socially aberrant behavior (for e.g., defecating/urinating in public, shouting at strangers, etc.)
      • Slurred speech
      • Muscle rigidity
  • Diagnostics
    • Elevated blood ammonia levels
    • Assessment of mental status
      • Number connection test: completed slower than the age-normalized standard or cannot complete
      • Psychometry‑based diagnostic method (e.g., Mini‑Mental State Examination, MMSE)
  • Treatment
    • General measures
      • Avoidance of trigger substances (e.g., hepatotoxic medication, alcohol)
      • Treatment of further complications which might aggravate HE (see “Triggers” above)
    • Lactulose: synthetic disaccharide laxative
      • First-line treatment for HE
      • Improves HE by decreasing absorption of ammonia in the bowel: lactulose is converted to lactic acid by intestinal floraacidification in the gut leads to conversion of ammonia (NH3) to ammonium (NH4+) → ammonium is excreted in the feces → decreased blood ammonia concentration
    • Rifaximin [21]
      • Non‑absorbable antibiotic
      • May be added to lactulose to prevent recurrent episodes of HE after the second episode

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

Hepatorenal syndrome (HRS)

References:[29][30]

Portal vein thrombosis

References:[31][32]

Pulmonary complications of portal hypertension

References:[33][34]

Prognosis

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

References:[9]