REFERAT HEPATORENAL SYNDROME

PEMBIMBING : dr. Sahala Panggabean SpPD KGH

PRESENTAN : Ilham Suryo Wibowo Antono

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

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)

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

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

Diagnostic CriteriaMajor 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

Diagnostic CriteriaMinor 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

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

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

Ascites and OedemaHRS

Portal Hypertension

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

Treatment of HRS

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

• TIPS• Liver Transplantation

REMEMBER!

VASOKONSTRIKTORALBUMIN

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

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

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

Terlipressin in HRS

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%.

• 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

TIPS

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

Encephalopathy Shunt stenosis Haemolysis Hyperbilirubinaemia

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

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

Thank You