Hepatorenal syndrome

Definition

• • Development of renal failure in patients with severe liver disease (acute or chronic)

    • In the absence of any other identifiable cause of renal pathology

Risk Factors

• • Strong

    • Advanced cirrhosis

    • Ascites

    • Alcoholic hepatitis

    • Acute liver failure

    • Hyponatraemia

    • High plasma renin activity (PRA)

    • Spontaneous bacterial peritonitis

  • Weak

    • Large volume paracentesis

    • GI bleeding

Differential diagnosis

• • Pre-renal azotaemia

  • Acute tubular necrosis - ischaemic

  • Acute tubular necrosis - nephrotoxic

  • Obstructive renal nephropathy

• Glomerulonephritis

Epidemiology

• • The probability of developing HRS in patients with cirrhosis is approximately 40% in 5 years

  • It occurs in 4% of patients admitted with decompensated cirrhosis

Aetiology

• • HRS may develop spontaneously in patients with cirrhosis

    • No objective criteria for a precipitating event other than progressive liver failure

  • May also develop in other chronic liver diseases associated with severe liver failure and portal hypertension

    • Alcoholic hepatitis

    • Acute liver failure

  • Cirrhosis is most commonly a result of infectious hepatitis or chronic alcoholism

  • Independent predictive factors of HRS occurrence are:

    • Low serum sodium concentration

    • High plasma renin activity

Clinical features

• • Key features:

    • Advanced cirrhosis (common)

    • Jaundice (common)

    • Ascites (common)

  • Other diagnostic factors

    • Moderate lowering of BP (common)

    • Peripheral oedema (common)

    • Hepatosplenomegaly (common)

    • Spider angioma (common)

    • Oliguria (uncommon)

    • Bruising (uncommon)

    • Petechiae (uncommon)

    • Palmar erythema (uncommon)

    • Scratch marks (uncommon)

    • Gynaecomastia (uncommon)

    • Encephalopathy (uncommon)

    • Pruritus (uncommon)

    • Confusion (uncommon)

    • Drowsiness (uncommon)

Pathophysiology

• • Four primary factors are involved in the pathophysiology of HRS:

    • Systemic vasodilation

      • Leads to a moderate lowering of blood pressure

    • Activation of the sympathetic nervous system

      • Leads to renal vasoconstriction and altered renal autoregulation

      • Causes renal blood flow to be much more dependent on mean arterial pressure

    • Relative impairment of cardiac function

      • Although cardiac output may increase, it cannot increase adequately to maintain blood pressure

      • In cirrhosis, this is termed cirrhotic cardiomyopathy

    • Increased formation of renal vasoconstrictors

      • Thromboxane A2, F2-isoprostanes, endothelin-1, cysteinyl-leukotrienes

      • Their exact role in the pathogenesis of HRS is unclear

Investigations

• • Creatinine

    • Rapid deterioration in patients with type 1 HRS

    • Slower course (deteriorating over several months) in type 2 HRS

  • Urea

    • May be artificially decreased because of reduced hepatic synthesis of urea

    • May be increased if GI haemorrhage

  • Electrolytes

    • Low sodium due to chronic liver disease

    • Potassium increases as renal failure progresses

  • FBC

    • Anaemia and thrombocytopenia due to chronic liver disease

    • An elevated WBC count is suggestive of the presence of an infection

      • May be responsible for the worsening renal function

  • LFTs

    • Transaminases, gamma-GT, and Alk phos may be normal or elevated in chronic liver disease

    • Low albumin is an indication of impaired liver function

  • Coagulation study

    • Indication of impaired liver function

  • Diagnostic paracentesis and culture of ascitic fluid

    • Elevated WBC suggests spontaneous bacterial peritonitis, which commonly precipitates HRS

  • Blood culture

    • Positive culture suggests sepsis

  • Urinalysis and culture

    • Presence of WBC and organisms indicates a possible infective cause of worsening renal function

    • Presence of RBC and red cell casts suggests an intrinsic renal cause of the renal failure

      • e.g. glomerulonephritis

    • Urinary sodium is low in HRS

      • Due to preserved tubular function and activation of sodium-retaining systems

      • Should not be used as a major criterion to differentiate between HRS and acute tubular necrosis

  • CXR

    • CXR is performed to exclude sepsis

Management

a) conservative

• • Supportive therapy

    • Patients should have their fluid status, urine output, and serum electrolytes monitored closely

    • In particular, patients should be prevented from developing severe hyponatraemia

      • But rapid correction of hyponatraemia is avoided

        • May lead to demyelination syndrome and increased ascites formation

    • If tense, symptomatic ascites is present, paracentesis may temporarily improve renal function

    • If severe electrolyte disturbances, volume overload, or metabolic acidosis is present:

      • Patients are considered for continuous haemofiltration

      • However, limitations such as hypotension make it difficult in this patient group

    • Immunisation with influenza and pneumococcal vaccines is important

      • These patients are immunocompromised

b) medical

• • Terlipressin

    • Terlipressin (a vasopressin analogue) plus albumin is the first-line therapeutic approach for type 1 HRS

    • It may prolong short-term survival, and reverse type 1 HRS

    • Treatment should target a serum creatinine of <133 micromol/L (<1.5 mg/dL)

  • Fluid bolus

    • If renal failure is due to hypovolaemia, it will improve after fluid bolus

    • No improvement will occur in patients with HRS

  • Antibiotics

    • Broad-spectrum non-nephrotoxic antibiotics such as ceftriaxone should be commenced

    • Continue until results of cultures are known

    • Negative cultures and persisting renal impairment indicate HRS

  • Albumin

    • Combined treatment with albumin and antibiotics reduces the incidence of renal impairment and death

  • Pentoxifylline

    • Improves short-term survival in patients with severe alcoholic hepatitis

    • Appears to be related to a decreased risk of developing HRS

  • Octreotide + midodrine + albumin

    • Midodrine is a vasoconstrictor, while octreotide inhibits release of endogenous vasodilators

    • These drugs work synergistically to improve renal haemodynamics

    • Usually only used as a bridging therapy until liver transplantation is available

c) surgical

• • Transjugular intrahepatic portosystemic shunt

    • Used in patients without severe liver failure in whom vasoconstrictors have failed to improve renal function

      • High serum bilirubin, Childs-Pugh score >12, severe hepatic encephalopathy

    • Functions as a side-to-side portocaval shunt and serves to relieve portal hypertension

    • Performed under analgesia

    • Placement of a self-expandable metal stent between a hepatic vein and the intrahepatic portion of the portal vein

      • Uses a transjugular approach

    • Usually only used as a bridging therapy until liver transplantation is available

  • Liver transplantation

    • Liver transplantation is the only definitive treatment of HRS

    • The decision for transplantation of a limited resource is complex and involves severity of illness and likely prognosis

    • Patients with severe co-morbidities are not candidates for a liver transplant

    • e.g. CAD or heart failure, advanced age, alcoholism, and infection

Prognosis

• • Prognosis for patients with HRS is poor

    • Type 1 HRS has a hospital survival of less than 10%, and median survival time is 2 weeks

    • Type 2 HRS has a median survival time of around 6 months

  • The severity of underlying liver disease is a factor in the ability to recover from the renal failure

  • The 1-year survival for type 2 HRS is 38.5%

  • In patients with HRS, the 5-year survival following liver transplant is around 60%

    • This is significantly lower than in patients without HRS (68%)