Chronic liver failure

Section: Hepatobiliary Sub-section: Liver Curriculum: Curriculum, page 72, Curriculum, page 87

Definition

• Chronic liver failure
  • A gradual and incremental liver cell mass and function due to repeated cell injury and attempts are repair. These to fibrosis and scarring, leading to cirrhosis.
• Cirrhosis
  • A diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules (regenerative nodules), resulting in impaired liver function and blood flow.
• Compensated and decompensated liver cirrhosis  
  • Compensated - Patients with liver cirrhosis who have not had any complications (NB: presence of varices which haven’t bled is still compensated cirrhosis) 
  • Decompensated - patients with liver cirrhosis and a complication including variceal haemorrhage, spontaneous bacterial peritonitis, hepatorenal syndrome, ascites

Aetiology

• Viral – hepatitis B/C
• Autoimmune – PBC, PSC, autoimmune hepatitis
• Alcoholic liver disease
• Metabolic – Wilson’s disease, α1-antitrypsin deficiency, NASH

Pathophysiology

• Repeated injury - regardless of cause
• Leads to hepatocyte death and inflammation
• With subsequent regeneration
• This repetitive process leads to replacement of the parenchyma with diffuse fibrosis and the presence of regenerative nodules
• This ultimately leads to cirrhosis which is characterised by
  • Diffuse fibrosis, architectural distortion, increased vascular resistance and nodular regeneration
• The consequences of this are (see below what is normal):
  • Portal hypertension
  • Synthetic dysfunction
  • Immune dysfunction
  • Metabolic dysfunction
  • Detoxification impairment
  • Excretory dysfunction
  • Progression to decompensation/end stage liver failure

Clinical

• Signs and Symptoms of Chronic Liver Disease
  • Spider nevi
  • Palmar erythema
  • Nail changes
  • Hypertrophic osteoarthropathy
    • Chronic proliferative periostitis of the long bones that can cause considerable pain.
  • Xanthelasma
    • Esp. with cholestatic liver disease
  • Loss of body hair
  • Dupuytren’s contracture
  • Gynaecomastia
    • Increased estradiol, up to 66% of pts
  • Hypogonadism
    • Impotence
    • Infertility
    • Loss of sexual drive
    • Testicular atrophy
    • Liver size
      • Can be enlarged, normal, or shrunken
  • Splenomegaly
    • Congestion of the red pulp
  • Ascites
    • Need 1500 mL to detect flank dullness
  • Caput medusa
  • Cruveilhier-Baumgarten murmur
    • Venous hum heard in epigastric region because of caput medusa
  • Fetor hepaticus
    • Musty odor in breath as a result of increased dimethyl sulfide
  • Jaundice
  • Asterixis
• Spider Nevi
  • Spider angiomata or spider nevi
  • Vascular lesions consisting of a central arteriole surrounded by many smaller vessels
    • Due to an increase in estradiol
    • These occur in about 1/3 of cases
  • In distribution of SVC
• Palmar Erythema
  • Exaggerations of normal speckled mottling of the palm
    • Due to altered sex hormone metabolism
• Nail Changes
• Muehrcke’s lines
  • Paired horizontal bands separated by normal colour
  • Resulting from hypoalbuminaemia
• Terry’s nails
  • Proximal two-thirds of the nail plate appears white with distal one-third red
  • Also due to hypoalbuminaemia
• Clubbing
  • Angle between the nail plate and proximal nail fold > 180 degrees
• Dupuytren’s Contracture
  • Thickening and shortening of the palmar fascia that leads to flexion deformities of the fingers
  • ? Fibroblastic proliferation & disorderly collagen deposition.
  • 33% of patients
  • More common in alcoholic liver disease
• Asterixis
  • Bilateral asynchronous flapping of outstretched, dorsiflexed hands
  • Seen in patients with hepatic encephalopathy
  • Prelude to ataxia, rigidity, convulsions & coma

Scoring system

MELD (Model for End-stage Liver Disease)

• Developed to predict mortality after TIPS
• Linear regression model

Included:

• Serum creatinine

• Total bilirubin

• INR

• MELD = 3.78(Lnserumbilirubin(mg/dL)) + 11.2(LnINR) + 9.57(Lnserumcreatinine(mg/dL)) + 6.43

  • Maximum score 40.
  • For consideration of liver transplant
  • MELD score >25 is 100% 1 year mortality

Child-Pugh score

Measure	1 point	2 points	3 points	Units
Bilirubin (total)	< 34 (< 2)	34–50 (2,3)	> 50 (> 3)	μmol/L (mg/dL)
Serum albumin	> 35	28–35	< 28	g/L
INR	< 1.7	1.71–2.20	> 2.20	No unit
Ascites	None	Suppressed with medication	Refractory	No unit
Hepatic encephalopathy	None	Grade I–II (or suppressed with medication)	Grade III–IV (or refractory)	No unit

• A = 5-6 points
• B = 7-19 points
• C = 10-15 points

Pathophysiology

Normal function

• Metabolism
  • Carbohydrate metabolism
    • Cori cycle:
      • Anaerobic metabolism of glucose to lactate (mostly in skeletal muscle), then liver converts back to glucose.
      • Failure of this causes lactic acidosis and hypoglycaemia
  • Protein metabolism
    • Liver breaks down protein and amino acids and clears nitrogen.
  • Lipid metabolism
    • Synthesis of cholesterol
• Synthetic function
  • Coagulation
    • Liver makes coagulation factors and fibrinolytic proteins – increased risk of bleeding AND thrombosis.
    • Impaired bile salt excretion impairs absorption of Vitamin K – Vitamin dependent factors are reduced – 10, 9, 7 and 2. Liver also makes protein C and S which are antithrombotic factors (thus you have a tendency to clotting)
  • Immune function
    • Creates acute phase proteins (i.e. CRP)
    • Innate immune cells (produces Kupfer cells which is part of the reticuloendothelial system).
    • Also produces opsonin’s which allows phagocytosis
  • Albumin
• Detoxification
  • Urea cycle
    • Ammonia is produced as biproduct of enterocyte metabolism.
    • Normally liver converts ammonia to urea which allows urinary excretion.
    • In liver failure ammonia builds up – hepatic encephalopathy. Treatment is lactulose (lactulose reduces the absorption of ammonia in the gut)
  • Drugs and toxins
  • Hormones
• Excretory function
  • Bile production
• Causes of death
  • Bacterial infection
    • Immune function compromised as liver’s phagocytic and synthetic capacity
  • Hepatic encephalopathy
    • Multifactorial.
    • Cerebral oedema
    • Raised ICP
      • Brain herniation & death

Liver assessment

• MELD/CPS
• Bloods:
  • Platelets, PT
  • LFTs
    • ALT/AST – transaminases secreted by hepatocytes
    • ALP – biliary epithelium
    • GGT both hepatocytes and biliary epithelium
  • Albumin, lactate, glucose, ammonia

Volume

• Measuring liver volume using CT or MRI

Liver function

• Substance clearance tests
• Indicator of dynamic function.
  • Indocyanine green clearance test
  • Hepatobiliary scintigraphy with radioisotope clearance (SPECT – combined with CT)
  • Lidocaine clearance.

Liver blood flow

• Measuring liver blood flow: Intraop doppler USS

Regenerative capacity

• Full liver function and volume are usually restored within 6–12 weeks in humans.
• In chronic injury or in the presence of fibrosis, liver regeneration can be chaotic with repeated insults causing scarring, and nodular regeneration with disordered architecture leading to cirrhosis.
• Assessing regenerative capacity – mitotic rate post resection

Assessment of steatosis

• difficult
• Can be judged by size, rounded or sharp edges of liver and its appearance.
• Gold standard is histology – trucut or wedge biopsies.

Measure hepatic wedge pressure: measure hepatic vein free and wedge 🡪 this can differentiate between pre, intra and post sinusoidal.>)

Operating on a patient with cirrhosis

• Complications of cirrhosis:
  • Ascites – consider paracentesis, fluid/sodium restriction
  • Variceal bleeding risk – beta blocker, gastroscopy/banding, TIPS
  • Encephalopathy – lactulose, rifaximin
  • Nutrition
  • Other comorbidities
• Anaesthetic considerations:
  • Cardiac dysfunction
  • Hypoxia
  • Hypotension, intravascular volume
  • Sepsis
  • Portopulmonary hypertension
  • Drugs – hepatotoxicity
• Operative risks
  • Assessment of severity
    •  Child-Pugh
      • Mortality in major abdominal surgery
        • A - 10%
        • B - 30%
        • C - 80%
    • MELD
      • Mortality
        • 1% increase each one-point increase from 5 to 20
        • 2% increase for each one-point increase above 20
  • Post-operative complications
    • Bleeding/coagulopathy
    • Wound complications – infection, impaired healing
    • Ascites leak
    • Sepsis
    • Decompensation of liver failure

Preop preparation

• Is operation needed? Is this time critical? Can liver disease be optimised?
• Is there time to transfer to an HPB unit
• MDT – hepatologist, anaesthetist.
• Optimisation
  • Manage ascites
    • Paracentesis
    • Sodium restriction
    • Diuretics
    • TIPSS
  • Variceal bleeding risk
    • NSBB
    • Banding
    • TIPS
  • Encephalopathy
    • Lactulose
    • Rifaxamin
  • Nutrition
    • B12/Folate/ Vit ADKE
    • Macro
    • Dietican review
    • Low salt and high energy diet
  • Coagulation
    • Coagulopathy in cirrhosis
    • Imbalance between anti/pro clot
    • Normal clotting tests dont always show an issue
    • TEG is the best to monitor
  • Renal function
  • Electrolytes
  • Other comorbidities
• Planning
  • Cross section imaging to help operative planning
  • Bail out strategy
  • TIPS/shunt if severe bleeding
• Prior to surgery
  • G&H +/- transfusion
  • HDU/ICU support
  • Hepatology review

Intra-operative

• Prophylactic antibiotics
• Entry
  • Port
    • Recanalised umbilical veins
    • Place your port away from the umbilicus
    • Or divide/energy device them
  • Avoid transverse incisions
    • More likely to divide varices
• Manage ascites
  • Suction out if present
  • Consider leaving and train vs intermittent ascitic tap
• Minimise dehiscence risk
  • Close all layers including peritoneum
• Bail out
  • Leaving the back wall of the gallbaldder on
• Bleeding
  • Use a ligasure

Postop care

• Aware of risk of decompensated liver failure
  • Stress response to pathology, surgery, GA, fluid shifts
• Risk factors for decompensation:
  • Dehydration
  • Constipation
  • Bleeding
  • Infection e.g. SBP
• Monitor bloods: Bili / INR / LFTs
• Monitor clinically for ascites and encephalopathy and treat appropriately
  • Ascites: Na restrict, diuretics, paracentesis if refractory
  • Encephalopathy: exclude other causes (e.g. hypoxia, hypercapnia, hypoglycaemia, uraemia, EtOH Withdrawal, ICH), treat with lactulose to ensure 2-3 BM per day
    • Lactulose acidifies colon and promotes conversion of ammonia to ammonium in bowel and not absorbed
• Monitor for Hepatorenal Syndrome
  • AKI but HD stable, no nephrotoxics and not improving
  • Treatment: Splanchnic vasoconstrictors (Terlipressin, Noradrenaline, Midodrine)
• Ensure VTE Prophylaxis
• Monitor for infection
• Be aware of complications unrelated to surgery:
  • Variceal bleeding
  • Volume overload
  • Portal Vein Thrombosis
• Be aware of poor wound healing secondary to malnutrition – ensure dietician involvement

Supportive management

• N-Acetyl cysteine
  • Initially used for paracetamol poisoning only.
  • Now used generally to replenish glutathione.
• Nutritional support
  • Enteral nutrition without excessive protein administration.
• Extracorporeal liver support:
  • Artificial liver support
    • MARS device.
      • Used albumin dialysis circuit to remove water soluble and protein-bound toxins.
  • Bioartificial liver systems
    • HepatAssist device
      • human hepatoblastoma cell lines
    • ELAD (Extracorporeal Liver Assist Device)
      • porcine hepatocytes

From Adam Bartlet Talk Note phosphate falls

Meld - 10 or more try and avoid

PH on imaging - 13cm spleen length or PV >13mm diameter