• Clinical science

Cirrhosis

Abstract

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

The diagnosis of cryptogenic cirrhosis should be considered only after a thorough, complete evaluation of the patient rules out all other possible causes as the etiology for the cirrhosis.

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. Established indications for biopsy are the following:
  • Execution:
    • Usually ultrasound‑guided transcutaneous approach: easily performed, but may have limited diagnostic value if only a small tissue sample can be taken
  • Alternative methods
    • Laparoscopic biopsy
    • Transjugular biopsy (transvenous biopsy)

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)
  • Elastography
    • Ultrasound modality that measures liver elasticity and helps assess the liver status over the course of the disease; e.g., ARFI (Acoustic Radiation Force Impulse; Virtual Touch®) and transient elastography (Fibroscan®)
  • Gastroscopy
    • Used to diagnose esophageal varices
    • Used to examine patients with portal hypertensive gastropathy
  • Factors promoting disease progression:
    • Alcohol use and smoking
    • Non‑alcoholic fatty liver disease
    • Hepatitis B
    • Hepatitis C
    • Gene analysis of the PNPLA 3 gene (adiponutrin) in alcoholic and non‑alcoholic fatty liver disease

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

Checklist for diagnosing liver cirrhosis

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
Micronodular 1–3 mm
Macronodular > 3 mm
  • Following diffuse parenchymal necrosis with relapses or acute course; e.g.:
Both 1–3 mm and > 3 mm
  • Possible in every type of liver‑damaging disease
  • Histopathological characteristics
    • Fibrous septa
    • Abnormal cell activation with infiltration of inflammatory cells
    • Loss of physiological vessel architecture (central vein disappearance)
  • See also

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)
    • Critical Flicker Frequency (CFF)
    • EEG
  • Rare differential diagnoses: hepatic myelopathy treatable only with a liver transplant.
  • Classification of disease severity according to West‑Haven
Clinical findings Other findings
Stage 0
  • Asymptomatic

Psychometric tests normal

Stage I
  • Mild lack of awareness
  • Attention span is shortened
  • Impaired ability to add and subtract
  • Asterixis is possible

EEG: triphasic waves

Stage II
  • Apathy/lethargy
  • Disoriented, inappropriate behavior
  • Slurred speech
  • Asterixis
Stage III
Stage IV EEG: delta activity
  • 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
      • Broad spectrum antibiotics: in gastrointestinal bleeding

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

Mortality (risk assessed according to clinical criteria)

1% mortality in stable patients without decompensation, esophageal varices, and ascites.

References:[9]