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Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

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Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit http://hepatologist.eu
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Page 1: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Hepatorenal SyndromeDr Allister J Grant

Leicester Liver Unit

http://hepatologist.eu

Page 2: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

History1863: Absence of histological changes to

the kidney in some cirrhotics with renal failure

1956: 1st detailed description of the syndrome by Hecker and Sherlock

1960s: Reversal of renal failure with kidney transplant to patients with CKD

1970s: Reversal of HRS with liver transplantation

Page 3: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Definition of HRS• Functional renal failure

– Absence of Histological changes

• Occurs in patients with chronic liver disease

• Progressive liver failure and ascites

• Can occur acutely in certain settings – Spontaneous bacterial peritonitis – Large volume paracentesis without albumin

• Marked renal vasoconstriction

• Reduced GFR

Page 4: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Hepatorenal Syndrome• Hepatorenal Syndrome is a severe complication of end stage

liver disease associated with an 80%-95% mortality at 2 weeks.

• The only interventions that have been shown to improve survival are liver transplantation and more recently the vasopressin analogues and TIPS

• Type 1 (Acute)

• Type 2 (Chronic)

Page 5: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .
Page 6: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Clinical Types of HRS

• Type 1 • Rapid decline in renal function• Doubling of serum Cr >132 or reduction in 24h

CrCl to <40ml/min• Less than 2 weeks• Spontaneous • Associated with SBP (20%) or large volume

paracentesis w/o albumin (15%)

Page 7: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

• Type 2

• Slower decline in renal function • Criteria for type 1 HRS not met • Development of diuretic resistant or

refractory ascites

Clinical Types of HRS

Page 8: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Epidemiology• Incidence

7-10% in hospitalized cirrhotics with ascites 20% at 1 year, 40% at 5 years

• Risk Factors Advanced ascites (diuretic resistant) Large volume paracentesis w/o albumin (15%) SBP (20%)

• Prognosis Worst prognosis of all complications of cirrhosis Type 1 median survival: <2 weeks Type 2 median survival: ~6 months

Page 9: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Diagnosis• Lack of specific testing

• Diagnosis of exclusion

• Differential Diagnosis of renal failure in cirrhosis

– Hypovolaemia (GI hemorrhage, shock)– Nephrotoxins (drugs, contrast)– Glomerulonephritis (Hep B and C)– Acute Tubular Necrosis – Obstruction

Page 10: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Diagnostic Criteria

Major Criteria

• Chronic or acute liver disease with advanced liver failure or portal hypertension

• Low GFR (Cr > 132mol/L OR CrCl < 40mL/min)

• Exclusion of shock, ongoing bacterial infection, volume depletion, and use of nephrotoxic drugs

• No improvement in renal function despite stopping diuretics and volume repletion with 1.5L of saline

• No proteinuria or ultrasonographic evidence of obstruction or parenchymal renal disease

Arroyo et al; Hepatology 1996; 23: 164-76

Page 11: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Diagnostic Criteria

Minor Criteria

• Urine volume < 500mL/day

• Urine sodium < 10mEq/L

• Urine osmolality > plasma osmolality

• Urine RBCs < 50 per hpf

• Serum sodium < 130mEq/LArroyo et al; Hepatology 1996; 23: 164-76

Page 12: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Pathophysiology

Splanchnic arteriolar vasodilatation

– Decreased effective arterial volume (EAV)– Decreased systemic vascular resistance– Hypotension– Activation of vasoconstrictor systems

– Renin-Angiotensin Angiotensin-Aldosterone-System– Sympathetic Nervous System– Anti-Diuretic Hormone

Page 13: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Pathophysiology

Hyperdynamic circulation

• Hypotension from reduced effective art vol • Low systemic vascular resistance (SVR)• Baroreceptor activation • SNS activation leading to increased

contractility • Increased cardiac output

Page 14: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Pathophysiology of CLD

Peripheral and splanchnic arterial dilatation

Reduced effective blood volume

Activation of renin-angiotensin-aldosterone systemSympathetic nervous systemADH

Na retention &Water retention

Low urinary NaDilutional hyponatraemia

AscitesSchrier et al Hepatol 1988

Plasma volume expansion

Renal vasoconstrictionReduced GFR

NSAIDAminoglycosides

Diuretics Sepsis

NaCl

Ascites and OedemaHRS

Portal Hypertension

Page 15: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Treatment of HRS

• Vasoconstrictors– Often combined with albumin– Vasopressin analogues (Terlipressin)

• TIPS• Liver Transplantation

Page 16: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Terlipressin

• Synthetic vasopressin analogue• Most studied drug for treatment of HRS

• Mechanism: V-1 receptor agonist • Splanchnic vasoconstriction• Adverse events (arrhythmia, ischemia)

<5%• IV bolus dosing

Page 17: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Pathophysiology of CLD

Peripheral and splanchnic arterial dilatation

Reduced effective blood volume

Activation of renin-angiotensin-aldosterone systemSympathetic nervous systemADH

Na retention &Water retention

Low urinary NaDilutional hyponatraemia

AscitesSchrier et al Hepatol 1988

Plasma volume expansion

Renal vasoconstrictionReduced GFR

Ascites and OedemaHRS

Portal Hypertension

Vasopressin

Increased blood vol

Page 18: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Meta-analysis: terlipressin therapy for the hepatorenal syndromeF. Fabrizi, V. Dixit & P. Martin APT 2006 24:935-44

Terlipressin in HRS

Page 19: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Meta-analysis: terlipressin therapy for the hepatorenal syndromeF. Fabrizi, V. Dixit & P. Martin APT 2006 24:935-44

Terlipressin in HRS

The pooled rate of patients who reversed hepatorenalsyndrome after terlipressin therapy was

0.52 (95% CI, 0.42; 0.61), P =0.0001; I2= 24.6%.

The pooled frequency of responder patients who showedhepatorenal syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P =0.00001; I2= 44.3%.

Page 20: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

• Six randomised trials were eligible for inclusion

• 3 trials (total 51 patients) assessed terlipressin 1 mg bd for 2 to 15 days

• Co-interventions included albumin, fresh frozen plasma, and cimetidine

• Terlipressin reduced mortality rates by 34%

• The control group mortality rate was 65%

• Terlipressin improved renal function assessed by creatinine clearance, serum creatinine and urine output

2009

Page 21: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

TIPS

• Reduce portal hypertension • Increase effective arterial volume• Reverse splanchnic vasodilatation• Complications

Encephalopathy Shunt stenosis Haemolysis Hyperbilirubinaemia

Page 22: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .
Page 23: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Liver Transplantation• Treatment of choice for HRS

• Limited by organ availability and mortality of HRS

• Higher rate of complications: – Higher post operative mortality – More days in the ICU – Increased need for post-op RRT (35% vs. 5% w/o HRS)

• Improvement in renal function – Increased GFR post-op vs. decline in non-HRS pts – Lower overall GFR compared to non HRS pts

Page 24: Hepatorenal Syndrome Dr Allister J Grant Leicester Liver Unit .

Thank You


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