Chronic Liver Disease

End result of a process of progressive destruction and regeneration of liver parenchyma, leading to fibrosis and cirrhosis. Cirrhosis is:

Epidemiology and Risk Factors

Pathophysiology

Key pathophysiological processes relate impairment of key liver functions:

  • Metabolic
    • Clearance of vasoactive mediators
      Typically altered baseline haemodynamics:
      • ↑ CO
      • ↓ SVR
        • ↓ Vasopressor response
  • Synthetic
    • Coagulopathy
      ↓ Synthesis of both procoagulant (predominantly II, V, VII, X) and anticoagulant (protein C, protein S, antithrombin III) factors leads to:
      • Highly deranged clotting studies
      • Variable in vivo clotting activity
        Often normal behaviour in stable patients, but can easily become both prothrombotic or coagulopathic.

Aetiology

Common causes include:

  • Viral hepatitis
    • Hepatitis B
    • Hepatitis C
  • Autoimmune disease
  • Alcoholic liver disease

Rarer causes include:

  • Cholestasis
    • Primary biliary cirrhosis
    • Sclerosing cholangitis
  • Vascular
    • Venous obstruction
    • Budd-Chiari syndrome
  • Infiltrative
    • Amyloidosis
  • Drugs
  • Toxins
  • Metabolic diseases
    • Wilson’s Disease
    • Haemochromatosis
    • α1-antitrypsin

Clinical Manifestations

Classified into:

  • Hepatic
  • Extrahepatic
    • Cardiac
      Classically a hyperdynamic, ↑ CO, ↓↓ SVR (possibly ↓ BP despite ↑ CO) state.
    • Endocrine
      • Secondary hyperaldosteronism
    • Renal
      • Hepatorenal syndrome
    • GIT
      • Portal hypertension
        Portal pressure >10mmHg. Leads to:
        • Collateral venous circulation
        • Ascites
        • Splenomegaly
          Thrombocytopaenia due to sequestration.
        • Oesophageal varices
      • Delayed gastric emptying
    • Haematological
      • Anaemia
        Multiple potential causes:
        • GIT bleeding
        • Hypersplenic haemolysis
        • Malnutrition
        • Anaemia of chronic disease
      • Coagulopathy

Porto-pulmonary hypertension and hepatopulmonary syndrome are discussed later, under complications.

MELD Score

Uses:

  • Serum bilirubin
  • Serum creatinine
  • INR

Diagnostic Approach and DDx

Investigations

Bloods:

  • FBE
    • Anaemia
    • Thrombocytopaenia
  • Coagulation assays
    • PT
      Prognostic indicator, especially post-surgery in CLD.
  • UEC
    • Baseline renal function important

Management

Anaesthetic Considerations

End-stage liver disease associated with high perioperative morbidity and mortality.

  • A
    • Aspiration risk
      Due to delayed gastric emptying. Consider RSI.
  • B
    • Presence of ascites or pleural effusions
      Restrict alveolar ventilation, FRC, and predispose to atelectasis and hypoxia.
  • C
    • Presence of alcoholic cardiomyopathy
    • Typically hyperdynamic circulation
      High CO, low SVR.
  • D
    • Wernicke’s encephalopathy
    • Hepatic encephalopathy
  • E
    • Neuromuscular blockade
      • Non-depolarising agents:
        • Require ↑ doses
          Due to ↑ VD.
        • Aminosteroids have prolonged elimination
  • H
    • Coagulopathy

Marginal and Ineffective Therapies

Complications

  • B
    • Ascites
  • C
    • Hepatopulmonary syndrome
    • Porto-pulmonary hypertension
  • D
    • Hepatic encephalopathy
  • F
    • Hepatorenal syndrome
  • G
    • Variceal bleeding
      May be precipitated by infection due to an ↑ in sinusoidal and portal venous pressure. Therefore, patients with variceal bleeds should receive antibiotics.
    • Ascites
    • Spontaneous bacterial peritonitis
    • Hepatocellular carcinoma
    • Decompensation
  • I
    • Sepsis
      Infections are:
      • More common in patients with cirrhosis
        • Physical debilitation
        • Deconditioning
        • Malnourishment
        • ↓ Phagocytic function
      • Associated with higher mortality and morbidity
        Up to 70% mortality. Higher incidence of sepsis associated:
        • AKI
        • Encephalopathy
        • Coagulopathy
      • The highest cause of death in cirrhotic patients

Causative organisms (in order of likelihood) include:

  • E. Coli
  • S. Aureus
  • E. Faecalis
  • S. Pneumoniae
  • P. aeruginosa
  • S. Epidermidis

Management of gastrointestinal bleeding is covered under Gastrointestinal Bleeding.

Hepatorenal syndrome is covered under Hepatorenal Syndrome.

Hepatopulmonary Syndrome

Intrapulmonary shunt secondary to indiscriminate pulmonary vasodilation and angiogenesis. Hepatopulmonary syndrome:

  • Occurs in 20% of cirrhotic patients
  • Occurs due to ↓ hepatic clearance of endogenous vasodilators or ↑ nitric oxide synthetase activity, leading to:
    • Impaired hypoxic pulmonary vasoconstriction
    • ↑ Angiogenesis, producing AVM
  • Associated with high mortality
    • 15% at 90 days
    • 40% at 1 year
  • Overwhelming majority resolve following liver transplantation
    May take up to 1 year, indicating some degree of pathological vascular remodelling.

Porto-pulmonary Hypertension

Pulmonary hypertension in the setting of portal hypertension. Porto-pulmonary hypertension is:

  • An ominous finding
  • Secondary to:
    • ↓ Hepatic clearance of vasoconstrictors
    • Thromboembolic disease
  • Responsive to pulmonary vasodilators
    May require sustained (>3 months) treatment to effect remodelling.

Pulmonary hypertension not due to left heart failure (i.e. ↑ PAP with a normal PCWP and normal PVR) is common (20%) in patients presenting for liver transplant, but the majority reflects an ↑ in CO and is not in itself a poor prognostic sign.

Prognosis

Child-Pugh Score

This is included mostly for completeness, the Child-Pugh score is inferior to standard ICU scoring systems for outcome prediction.
MELD (see Scoring) is equally poor in predicting outcome in the ICU patient.

Score to assess prognosis of cirrhosis:

  • Initially developed to predict perioperative mortality
  • Validated for prognostication and to assess necessity of liver transplantation
Child-Pugh Score Components
Value 1 point 2 points 3 points
Total bilirubin (μmol/L) ⩽34 34-50 ⩾50
Serum albumin (g/dL) ⩾3.5 2.8-3.5 ⩽2.8
PT (s) ⩽4 4-6 ⩾6
INR ⩽1.7 1.7-2.3 ⩾2.3
Ascites None Mild/medically controlled Moderate to severe/refractory
Hepatic encephalopathy None Grade I-II Grade III-IV

There are many issues with the Child-Pugh score:

  • Subjective assessments have inter-observer variability
  • Evaluation of ascites has progressed since the ’60s when the score was developed
  • Excludes effects of concomitant disease

Patients are then risk stratified as follows:

Child-Pugh Scoring
Class Points One-year survival
A 5-6 100%
B 7-9 80%
C 10-15 45%

Key Studies

References

  1. Lata J. Hepatorenal syndrome. World J Gastroenterol. 2012 Sep 28;18(36):4978–84.
  2. Vaja R, McNicol L, Sisley I. Anaesthesia for patients with liver disease. Contin Educ Anaesth Crit Care Pain. 2010 Feb 1;10(1):15–9.