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

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%)