• Clinical science

Cirrhosis

Summary

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.

Epidemiology

  • Prevalence: approx. 0.27% in US adults [1]
  • Sex: > (2:1) [2]
  • Mortality [2]
    • 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.

Etiology

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.

Hepatitis C, alcoholic liver disease, and NASH are the most common causes of cirrhosis in the US.

Pathophysiology

Clinical features

Clinical manifestations of liver cirrhosis generally represent the severity of liver disease. [6]

Diagnostics

Laboratory tests [6]

Complete blood count (CBC)

Liver function tests

Other laboratory tests

Additional laboratory studies can be performed to determine the etiology of chronic liver disease.

Imaging studies

  • Abdominal ultrasound
    • Best initial imaging study
    • Liver form and structure findings
      • Nodular liver surface
      • Atrophy of the right lobe
      • Loss of structural homogeneity (hyperechoic or variable increase in echogenicity) with fibrous septa
    • Liver size findings
      • Initially enlarged
      • Atrophies and shrinks with disease progression
    • Other possible findings
  • CT scan
    • Typical findings
  • Transient elastography
    • Ultrasound technique used to measure liver elasticity
    • Allows for monitoring of patients with chronic liver disease and helps with early diagnosis of increased fibrosis and progression to cirrhosis

Biopsy

  • 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
    • Laparoscopic biopsy Large biopsies can be obtained.
    • Transjugular biopsy (transvenous biopsy)
      • For severely obese patients or patients with ascites.
      • There is a lower risk of bleeding in comparison to a standard biopsy.
      • A transjugular biopsy is especially useful if TIPS is planned.

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

Monitoring the disease course

Patients diagnosed with cirrhosis should repeat laboratory tests every 6 months to recalculate the Child-Pugh score and Model for End-Stage Liver Disease (MELD) scores (see “Prognosis” below).

Pathology

  • Fibrosis (fibrous septa)
  • Replacement of normal liver tissue with collagenous regenerative nodules (histological staging is based on the size of the regenerative nodules) [6]
  • Abnormal cell activation with infiltration of inflammatory cells
  • Loss of physiological vessel architecture (central vein disappearance)
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

General approach [10][11]

Pharmacotherapy

Surgical/Interventional procedures [12]

Complications

Cirrhosis associated ascites and edema, as well as the high risk of bleeding, increase the risk for hypovolemic shock.

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

Hepatic encephalopathy

Definition [13][11]

  • Fluctuations in mental status and cognitive function in the presence of severe liver disease (e.g., cirrhosis)

Pathophysiology [14]

Precipitant factors

Clinical features

Symptoms are usually reversible.

  • Fatigue, lethargy, apathy
  • Altered levels of consciousness, ranging from mild confusion to stupor or coma
  • Disoriented
  • Irritability
  • Memory loss
  • Impaired sleeping patterns
  • Multiple neurological and psychiatric disturbances
  • Socially aberrant behavior (e.g., urinating/defecating in public, shouting at strangers)
  • Slurred speech
  • Asterixis
  • Muscle rigidity

Diagnostics

Treatment

Hepatorenal syndrome (HRS)

Definition

  • Deterioration of kidney function in patients with advanced liver disease

Pathophysiology [17][18]

Risk factors

Generally attributed to the loss of volume

Clinical features [17]

Diagnosis

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 [19]
    • Cirrhosis
    • 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

Treatment

Portal vein thrombosis

Definition [20]

  • A complete or partial closure of the portal vein due to a thrombus

Pathophysiology

Etiology

Clinical features

Depend on the extent of thrombosis and the speed of manifestation

Diagnostics

When PVT is detected in patients with cirrhosis, HCC must be ruled out as the cause.

Treatment [21]

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.

Pulmonary complications of portal hypertension

Hepatopulmonary syndrome [23][24]

Definition

Pathophysiology

Clinical features

Diagnostics [25]

Treatment [24]

  • Supportive measures: Long‑term treatment with oxygen is recommended.
  • Surgical procedure: liver transplant

Portopulmonary hypertension [26][27]

Definition

Pathophysiology

Clinical features

Diagnostics

Treatment

Other pulmonary complications in cirrhosis

Prognosis

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 (MELD score) and Child-Pugh score systems. [10]

Child-Pugh score

  • 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
    • Can be used as a prognostic scoring system [29]
      • Child‑Pugh class A: almost normal
      • Child‑Pugh class B: one-year survival rate of approx. 80%
      • Child‑Pugh class C: one-year survival rate of approx. 45%
    • In patients with decompensated cirrhosis survival is poor, unless they receive liver transplantation.
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

CHILD's ABCDEs: Albumin, Bilirubin, Coagulation (e.g., INR), Distended abdomen (ascites), and Encephalopathy.

MELD score

  • 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.