HEPATORENAL SYNDROME

Dr.N.Praveen23-11-2011

HEPATORENAL SYNDROME

INTRODUCTION

• Hepato Renal Syndrome (HRS) is a functional and reversible form of renal failure , in patients with advanced chronic liver disease.

• Interactions between systemic and portal hemodynamics causes intense renal vasoconstriction .

• May develop spontaneously without known precipitating factors but there are known triggers.

• To be diagnosed based on criteria.• Worst prognosis of all the complications of cirrhosis.• Terlipressin is the drug of choice in treatment. • Liver transplantation is the definitive cure for patients. • Recently liver dialysis by means of albumin bound membranes is

providing a means of extracorporeal liver support.

History

• Frerichs ,Flint - first report of renal failure in the absence of significant renal histologic changes,in chronic liver diseases.

• Hecker, Sherlock (1956) – Pathogenesis of hepatorenal syndrome.

• Epstein et al - splanchnic ,systemic vasodilation together with intense renal vasoconstriction is the pathophyisological hallmark of HRS.

• 1970 s -TERMINAL FUNCTIONAL RENAL FAILURE• 2007 -Molecular Adsorbent Recirculating System.

Alternative names• Heyd's syndrome• Flint's syndrome • Frerichs' syndrome• Bile nephrosis,• Cholemic nephrosis,• Hepatonephrite, • Hepatonephritis serosa acuta,•  Leber-Nieren-Syndrom (German), • Nephrite fonctionelle (French). Friedrich T. von Frerichs

Case

• A 35-year-old male,k/c/o alcoholic cirrhosis, ascites and a history of alcoholic hepatitis presented to casualty for management of his cirrhosis and was diagnosed with new-onset renal insufficiency upon admission.

• no history of renal dysfunction ,diabetes mellitus. He had blood transfusions at another hospital 5 days previously after having suffered a gastrointestinal hemorrhage.

• No h/o SBP or recent treatment with nephrotoxic drugs. Upon admission, he was taking pentoxifylline 400 mg three times daily (tid) for alcoholic hepatitis, and furosemide 80 mg daily (qd) and spironolactone 200 mg qd for his cirrhosis with ascites.

• Physical examination revealed jaundice, ascites, and spider angiomas on his chest. Viral hepatitis serologies were negative, but ultrasound revealed a nodular liver and splenomegaly. No evidence of chronic renal parenchymal disease or obstructive uropathy. Ascitic fluid analysis demonstrated a SAAG of >1.1g/dl.

• Diuretics were discontinued, and intravascular volume replacement was provided by administration of both 1.5 l of isotonic saline and a total of 120 g of human albumin administered over several doses but the patients renal function continued to worsen.

• A DIAGNOSIS OF HEPATORENAL SYNDROME WAS MADE.

CAUSES OF RENAL FAILURE IN CIRRHOSIS

• Large volume paracentesis• Shock• Sepsis• Nephrotoxic Medications• Intrinsic renal diseases• Volume depletion secondary to diuresis.

HYPOTENSION

Renal failure

Diagnostic Approach to Renal Failure in Cirrhotics

Renal failure in a pt with cirrhosis

ECF fluid losses;rapid/excessive diureticsVomiting,diarrhoea,hemorrhage,recent,LVP /hemodynamic changes due to use of NSAIDS (or)ACEI

NO

YES

h

hold diuretics,offending medicationsTrial of ntravascularvolumeexpander(albumin)if renal function ↑ses ,Diagnosis of prerenal failure is made

Recent use of nephrotoxicmedications Hypotension(sepsis,hemorrhage)

Glomerular proteinuria&hematuriai.e.,dysmorphic RBCs and RBC cast

Toxic or ischemic renal failureYES

Suspected glomerular diseaseDepending upon clinical scenarioFurther workup may include Cryoglobulins C3,C4 and renal biopsy

YES NO

NO

Imaging (USG,CT scan)shows Hydronephrosis,urinary retention

Suggestive of obstructive uropathyUnless long standiing relief of obstructionShould lead to improvement in renalfunction

YES

Patient has evidence of Portal Hypertension & serum creatinine>1.5mg/dl

Diagnosis of HRS can be made

NOYES

IAC verbatim• “Hepatorenal syndrome is a syndrome that occurs

in patients with chronic liver disease, portal hypertension and advanced hepatic failure .It is characterised by impaired renal function, marked abnormalities in arterial circulation and activity of endogenous vasoactive systems . In the kidney ,there is marked renal vasoconstriction that results in low GFR. In the extrarenal circulation there is predominance of arteriolar vasodilation , that results in reduction of total systemic vascular resistance and arterial hypotension.A similar syndrome may also occur in the setting of acute live failure”.

-IAC ,Chicago 1996

• First systemic attempt to define HRS was made by International Ascites Club(1994)

• HEPATORENAL SYNDROME is a distinct form of fucntional acute/sub acute renal failure charecterised by severe renal vasoconstriction which develops in decompensated Cirrhosis or Acute liver failure,in the absence of uderlying renal pathology. (Clinics of North America;Expert consensus;1996)

• Recently updated to include Albumin as volume expander.

DEFINITION

• Incidence of HRS in patients with chronic liver disease is not well studied.

• 4% of patients admitted with decompensated cirrhosis.• In a study of 234 non azotemic patients with liver disease who

had ascites and cirrhosis,18% developed HRS at 1year and 39% developed by 5 years.

• Retrospective studies indicate HRS is present in 17% of pts admitted to hospital with ascites,and in > 50% of cirrhotics dying from liver failure

• Some patients without ascites devolped the condition in the setting of acute fulminant hepatic failure.

EPIDEMIOLOGY

Pathophysiology

• Four interrelated pathways have been implicated in the pathophysiology ..

• “Possible impact of each one of these pathways on renal vasoconstrcition and development of HRS varies from one patient to other .”

• 1.PERIPHERAL ARTERIAL VASODILATION• 2.STIMULATION OF RENAL SNS• 3.CARDIAC DYSFUNCTION• 4.CYTOKINES ,VASOACTIVE MEDIATORS.

Cont..

• 1.PERIPHERAL ARTERIAL VASODILATION : • Rational and simple explanation to the hemodynamic

changes that takes place in cirrhosis ,HRS.• Degree of hepatic decompensation

degree of hyperdynamic circulation ,

• Degree of hepatic decompensation 1/ arterial BP.

• Reversal of HRS ,improvement of hemodynamics by systemic vasoconstriction gives support to this hypothesis.

Pathophysiology of HRS

CIRRHOSIS splanchnic arterial vasodilation arterial underfilling

stimulation of systemic vasoconstrictors renal vasoconstriction

late stage of cirrhosis early stages of cirrhosis ¯ local vasodilators , local vasoconstrictors systemic and local ¯ vasodilators ¯ HEPATORENAL SYNDROME PRESERVED RENAL PERFUSION

Correlation between clinical features and pathophysiology in

HRS HRS diuretic refractory ascites ascites Clinical Physiological

Portal HTN Splanchnic vasodilation

renal vasoconstriction

• 2.stimulation of renal SNS :

• sympathetic tone in pts with cirrhosis.

• KOSTREVA et al vena caval ligation -- increased

intrahepatic pressure -- renal sympathomimetic

activity --wears after anterior hepatic nerves are cut.

• Severing renal ,hepatic,spinal nerves abolishes the

response of decreased GFR ,RPF seen after

hepatocyte swelling.

• 3.cardiac dysfunction :• Myocardial contractility impaired.( cirrhosis )• Diastolic dysfunction cirrhosis progression• Hyperdynamic state being present• Cause is diseased liver ,reversible after TRx• BNP , CVP child pugh score ,ventricular wall thickness.• Neurohormonal activity - growth ,fibrosis – disturbed

relaxation .• Inhibitory effect of TNF ,NO on ventricular function.

Cardiac dysfunction is masked by decreased afterload in cirrhotic patients .

Decreased cardiac output identifies group of patients at risk of HRS .

• 4.cytokines ,vasoactive mediators:• Not a sole player.• NO,TNF ,endothelin , endotoxin,glucagon,increased PG s .• Upregulation of e NOS activity,endotoxin ,inducible.• Reduces pressor effect of vasoconstrictors.• More in cirrhotics ,ascites.• Renal vasoconstriction due to dimethylarginine - a natural

NO inhibitor.• Reduced cyclooxygenase activity in renal medullary tissue.

Precipitating factors

• In type I HRS ppting event identified in 70-100 % pts.• More than one event in a patient.• Bacterial infections• Large volume paracentesis without albumin infusion.

(15%)• GI bleeding • Acute alcoholic hepatitis. (25%)• SBP - 20-30% develop HRS.

How ppt factor leads to renal failure?

• A.cytokine-induced aggravation of the circulatory dysfunction with further stimulation of the RAAS and SNS and worsening renal vasoconstriction.

• intrarenal vicious cycle that favors more renal vasoconstrictor release and impairs renal vasodilator synthesis .

• will progress to HRS even if the underlying precipitating event has been corrected.

• B.secondary to deterioration in cardiac function as a result of either the development of septic cardiomyopathy or worsening of a latent cirrhotic cardiomyopathy

DIAGNOSIS OF HRS• Diagnosis of HRS is made on certain predefined criteria

in the appropriate clinical setting• Increasing s.creatinine in patients with cirrhosis and

acute fulminant liver failure itself is enough to investigate for Hepatorenal syndrome

• All the major criteria are to be met for the diagnosis of HRS and minor criteria are just supportive and are not essential to make the diagnosis

MAJOR DIAGNOSTIC CRITERIA

1)Chronic/Acute liver disease with advanced hepatic failure or portal hypertension

2)Serum creatinine >1.5mg/dl(reflecting decreased GFR),<40 ml/min

3)Absence of shock,bacterial infection,current or recent treatment with nephrotoxic drugs,absence of renal or g.i.t losses

4)No increase in renal function after diuretic withdrawal and plasma volume expansion and intravenous albumin(1g/kg bdy wt upto a maximum of 100g)

5)Proteinuria <500mg/dl, no USG evidence of renal parenchymal damage (urine analysis) , no obstructive uropathy.

MINOR DIAGNOSTIC CRITERIA

Urine volume <500ml/24 hrUrine sodium <10 meq/LUrine plasma osmolality greater than plasma osmolalityUrine blood cells<50 per HPFSerum sodium <130 meq/L

CLASSIFICATION OF HRSClassified based on TIME COURSE and PRECIPITATING

FACTORSFour types-HRS type-1: Cirrhosis with rapidly progressive

acute renal failureHRS type-2:Cirrhosis with sub acute renal failureHRS type-3:Cirrhosis with type-1 or type-2 HRS

superimposed on chronic kidney disease/acute renal injury

HRS type-4:fulminant liver failure with HRS

Clinics of North America,2006

TYPE-1 HRS

It is the cirrhosis with rapidly progressive acute renal failureCharacterized by-Rapid elevation of BUN and creatinine:100% increase with a level reaching

2.5mg/dl in 2 weeks or a 50% reduction in initial 24 hr clearance to < 20 ml/min

Rapidly progressiveMortality reaching 80% with 2 weeksCommonly has precipitating factors-SBP(20%) -variceal hemorrhage -acute alcoholic hepatitis -drug induced(acetaminophen) -acute hepatic injury from viral hepatitisDeeply jaundiced ,coagulopathyDeath by hepatic plus renal failure,variceal bleeding.

TYPE-2 HRS

Cirrhosis with sub acute renal failureCharacterized by-Slowly increasing serum creatinine levels and slow

reduction of GFR(Takes weeks to months)No precipitating factorIt has poorer prognosis and eventually progresses to type -1

due to precipitating factors

TYPE-3 HRS

Cirrhosis with type 1 or type 2 HRS superimposed on chronic kidney disease or acute renal injury

85% of end stage cirrhotics have intrinsic renal disease on renal biopsy

Diagnostic markers of HRS are absent

TYPE-4 HRS

Fulminant liver failure with HRSMore than 50% of acute fulminant liver failure develop

HRSPrognosis of HRS is superimposed on already poor

prognosis of acute fulminant liver failure.

CLINICAL FEATURES

• SYMPTOMS- -distension of the abdomen -change in mental status(confusion,delirium and

dementia) -coarse muscle movements or muscle jerks -dark coloured urine -yellow skin -↓sed urine output -nausea and vomiting -weight gain

• SIGNS -Confusion - icterus - ascites - abnormal reflexes - decreased testicle size - gynaecomastia - sores on the skin

DIFFERENTIAL DIAGNOSIS

• Pre renal causes--- hemorrhage ,diarrhea,hypovolemia• Intra Renal causes --- acute tubular necrosis,interstitial

nephritis. • Post renal causes -- uropathy

• Diagnosis by exclusion.• it is extreme example of prerenal failure.(Una <20 ,Fna <1, Ucr/Pcr >40 ,Uosm/Posm >1.5 )

LABORATORY STUDIES

• Diagnosis depends mainly on s . creatinine levels as no specific tests establish the diagnosis of HRS. (>1.5mg/dl)

• Though serum creatinine level is a poor marker of renal function in cirrhosis (low muscle mass)no other validated and reliable non invasive markers exist for monitoring renal function in these patients.

• Inulin clearance is cumbersome and is not used clinically.• Low GFR is defined by s cr >1.5 mg/dl without diuretic

therapy for at least 5 days.• overestimates GFR by upto 50% .

CBP ,WBC : infection such as SBP if leucocytosis or bands are present,a condition known to present with reversible impairment in renal function

Serum electrolytes and renal function

Liver function test with PT (although the degree of liver failure doesn’t correlate with the development of HRS,these are essential for Child-Pugh scoring)

Blood cultures- for bacteremia particularly if no precipitant is identified,is prudent( 20% SBP are culture -ve)

Cryoglobulins- in patients with hepatitis B and or C who can develop renal failure from cryoglobulinemia.

MANAGEMENT

GENERAL MANAGEMENT:• Type I HRS - hospitalization, type 2 - outpatient.• CVP for assessing fluid status.• Stop diuretics• Tense ascites -paracentesis• If > 5l of fluid removed ,then albumin is good as

volume expander.• low salt diet,free water restriction -hyponatremia cases.• HRS type-1 & 4 need intensive management

THERAPUETIC OPTIONS

• Pharmacological treatment• Surgical• TIPS• Artificial liver support • RRT• Liver transplantation.• LKT

Pharmacological treatment

• Goal : reverse renal function• Prolong survival until liver TRx.• 1.RENAL VASODILATORS • 2.SYSTEMIC VASOCONSTRICTORS.

• 1.RENAL VASODILATORS:• DIRECT renal vasodilators - DOPAMINE,FENOLDOPAM,PGs• Antagonizing endogenous effect of renal vasocontrictors-

Sarlasin,ACEI ,endothelin antagonists.

DOPAMINE Low dose dopamine(2-5µgm/kg /min) is prescribed in the hope

that its vasodilatory properties may improve renal blood flowMISOPROSTOLA synthetic analogue of PG E1, use was based on the

observation of low urinary levels of vasodilatory PGs.The use of both the above drugs was not substanciated by any

studiesRENAL VASOCONSTRICTOR ANTAGONISTSarlasin used in attempt to reverse renal vasoconstriction.This inhibits the hemostatic response to hypotension and led to

further worsening of renal function .N-ACETYLCYSTEINEMechanism of action is unknown but studies encourage

optimism for medical management where option for liver transplant is not present

• None of the studies that used renal vasodilators showed imrpovement in renal perfusion or GFR. -- Barnado et al , Benette et al .

• Because of adverse effects ,lack of benefit the use of renal vasodilators has been abandoned.

Systemic vasoconstrictors

• Most promising agents.• Interruption of splanchnic vasodilation will relieve the

intense renal vasoconstriction.• VASOPRESSIN ANALOGUES -ORNIPRESSIN ,TERLIPRESSIN• SOMATOSTATIN ANALOGUE -OCTREOTIDE.• ADRENERGIC AGONISTS - MIDODRINE, NOREPINEPHRINE.

VASOPRESSIN ANALOGUES:• Marked vasoconstrictor effect.• V1receptors on smooth muscle of arterial wall .• Rx of acute variceal hemorrhage.• Ornipressin -- ischemic adverse effects. (30% ) • Terlipressin – most common used drug now.• Better response in type 2 HRS than in type 1 HRS.• 17-50% recurrence rate of HRS. – reversible.• Duration of therapy is unclear.• 60-80% improvement in type IHRS• To be given until s creatinine< 1.5 mg/dl ,or 15days.• Liver disease occurs in 3 months of therapy if not TRx.

OCTREOTIDE:• An inhibitor of glucagon.• Ineffective in type 2 HRS Alpha ADRENERGIC AGONISTS - MIDODRINE,NE• Both are ineffective in type 2 HRS .• Better response in type I HRS.

DRUG DOSE DURATION SIDE EFFECTS

TERLIPRESSIN 0.5-2mg every 4 hrs as IV bolus

15 days Peripheral,cardiac,splanchnic ishemia

NOREPINEPHRINE 0.5-3.0 mg/hr IV infusion

15 days same

MIDODRINE 7.5-12.5 mg every 8 hrs oral

?? Not reported

• High HRS recovery rate with vasopressin and improved survival ,more likely to recieve a liver transplant compared to octreotide - Kiser et al.

• Norepinephrine role is paradox - levels are elevated in pts with HRS.Significant improvement with albumin infusion in pts with HRS.

TREATMENT PROTOCOL OF NORADRENALINE/TERLIPRESSIN PLUS

AIBUMIN FOR HRS:

• NA –Initial dose 0.146µg/kg/min iv infusion,if no increase in MAP by 10mm Hg, dose by 0.05µg/kg/min every 4thhrly up to dose of 0.7µg/kg/min

• Terlipressin- 1mg iv bolus every 4th hrly.At day 3 if baseline s. creatinine not reduced ≥25% , the dose up to 2mg every 4thhrly

MIDODRINE WITH OCTREOTIDE

Midodrine(alpha adrenergic blocker) and octreotide (somatostatin analogue)

Rx protocol of midodrine plus octreotide therapyOctreotide initial dose:100µgm t.i.d SC goal to increase upto 200µgm t.i.d SCMidodrine Initial dose:5mg,7.5mg,10mg t.i.d orally goal to ↑dose upto 12.5mg to 15mg t.i.d if necessaryBecause of oral and subcutaneous route of the drug suitable

for use in outpatient deparment

CONTRAINDICATIONS OF VASOCONSRICTOR THERAPY:

• CAD• Cardiomyopathies,• Cardiac arrythmias,• Cardiac/respiratory failure,• Arterial HTN,• Cerebrovascular disease,• Peripheral vascular disease,• Bronchospasm,asthma,• Terminal liver disease,• Advanced hepatocellular carcinoma,• Age >70yrs

TIPS• Insertion causes reduction of portal pressure.• Beneficial in patients with cirhhosis and refractory ascites.• M.O.A- suppression of putative hepatorenal reflex,

improvement in circulatory volume,ameiloration of cardiac function.

• Guevara et al• Unanswered observations• 1 . Parameters improve,but not normalize. After TIPS.• 2.maximum renal recovery is 2-4 wks.• 3.advanced cirrhotic patients are not benefited.• 4.ppts underlying acute heart failure.

TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT(TIPS)

Is theoretically attractive therapyIt dramatically lowers portal pressure leading to ↓ pooling of

blood in splanchnic bedBut ↑venous return is inappropriately handled And many patients do not meet the criteria for TIPS insertion(i.e

serum bilirubin <5mg/dl,INR <2 and Child-Pugh score <12) When these conditions are not met TIPS insertion may lead to

liver failure or intractable hepatic encephalopathyDone only in patients with Child-Pughs A/B with criteria and

who do not respond to vasoconstrictor therapy Patients with refractory ascites often proceed to the

development of HRS type -2 and TIPS in these patients may lead better survival(metaanalysis)

SURGICAL CARE

PERITONEOVENOUS SHUNTINGtheoretically seems attractive because it leads to plasma

volume expansion and improvement of circulatory function

Has no role in type-1 HRSImportant for patients type-2HRS who have refractory

ascites and are not candidates for orthotopic liver transplant and do not tolerate frequent LVPs

ARTIFICIAL LIVER SUPPORT

Eliminates circulating mediators of splanchnic vasodilatation & renal vasoconstriction

Provides hemodynamic benefit and decreases s. creatinine Continous venovenous hemofilteration is better.In Acute liver failure patients treated with porcine

hepatocyte based bioartificial liver reported renal failure no details providedCurrently these are being used in HRS but are not

advocated for its treatment.

ALBUMIN DIALYSIS

• Currently three systems are available for albumin dialysis.• 1.MARS• 2.PROMETHEUS• 3.SINGLE PASS ALBUMIN DIALYSIS (SPAD)

MOLECULAR ADSORBENT RECIRCULATING SYSTEM

(MARS)• Designed by Stange and Mitzner from Germany in 1993.• Cell free ,modified dialysis technique.• Three circuits - blood,albumin,renal.• 600 ml of 20% albumin acts as dialysate• Removes both albumin bound,water soluble substances by

using a combination of albumin enriched dialysate,CRRT.• Removal of albumin bound bile acids (detrimental to

hepatocytes) ,kidney –stabilizes liver function.• Removes water soluble TNF A , IL6 and NO.• Substance . 50 KDa are not removed . Artif Organs 1993 ;17:809-13

PROMETHEUS

• First described in 1999 .• Principle of fractioned plasma seperation and adsorption.• Albumin permeable membrane ,size of 250kDa.• Albumin passes through the membrane and adsorbers that

remove toxins.• Reduction of both bilirubin,urea more > MARS.

Rifai K, Kretschmer U ,et al. J.Hepatol 2003 ; 39:984-90

SINGLE PASS ALBUMIN DIALYSIS(SPAD)

• Dialyses blood/plasma against a 4.4% solution of albumin,disposed after a sinlge pass.

• A standard renal replacement machine is used with out any additional perfusion pump system

• With regard to bilirubin,ammonia it is greater than MARS in its detoxifying capacity.

• In vivo useful in fulminant hepatic failure.• Further experience required for routine use.

Kreymann B, Schweigart U et al. J.Hepatol 1999;31:1080-5

RENAL REPLACEMENT THERAPY

• Controversial role in pts with type I HRS ,not undergoing liver TRx.

• To be individualized.• Indications:• 1.waiting for liver TRx• 2.developed volume overload• 3.intractable metabolic acidosis.• 4.hyperkalemia.• Bridge to liver TRx.• CRRT > HD - removes inflammatory cytokines - TNF A,IL-6• FUTILE IN pts on mechanical ventilator.

LIVER TRANSPLANTATION

• Best treatment for suitable patients with HRS.• RENAL SODIUM excretion,hemodynamic abnormalities

normalize in 1 month.• Renal resistance index normalize in 1 year post

transplantation.• Allocation is by MELD score.• Alessandra et al MELD score not beneficial for HRS pts.• Prolonged hospitalizations required• Renal failure persists for weeks post TRx.• Post TRx reversal of HRS is 58%.

LIVER TRANSPLANT

Long term survival following liver transplant is goodMortality of individuals with HRS was as high as 25% within the

first month after transplantation(HRS patients with grater hepatic dysfunction MELD score >36 are at greater risk of early mortality)

high priority is given to type-1But these patients are not transplanted because of the

precipitating event which initiated HRS and are extremely ill with multiorgan failure and rapid course of the disease providing insufficient time

In patients with HRS type -2 liver transplant is more practical because of the absence of precipitating factors,longer clinical course & less severe renal failure

In type-3 HRS both liver and kidney transplant in these extremely ill patients is a dilemma.

only liver transplant may be beneficial given the prospect of post op RRT

Patients with low MELD score and successful vasoconstrictor therapy have lower post op complications.

Further deterioration of renal function after liver transplantation is transient and is thought to be due to use of immunosuppressants that are nephrotoxic(tacrolimus, cyclosporin)

Renal function before liver TRx is an independent predictor of both short term and long term post transplantation patient and graft survival…Gonwa et al

Predictors of renal recovery

• Younger recipients• Nonalcoholic liver disease• Low posttransplantation bilirubin• Age of the donor

LKT

• Prolonged duration of RRT pretransplantation.• h/o previous renal failure• CKD on biopsy.

SPECIFIC THERAPY

TYPE OF HRS

TREATMENT

TYPE I HRS Vasoconstrictors,albumin,TIPS,liver Trx

TYPE 2 HRS Vasoconstrictors ,LVP,TIPS(ref),Liver Trx

TYPE 3 HRS CRRT, LKT TYPE 4 HRS idealy LTx

PREVENTIONPrompt treatment of precipitating factors of type-1 HRS

like sepsis, shock, variceal hemorrhage,acute alcoholic hepatitis and nephrotoxic drugs according to standard guidelines

A trial has shown norfloxacin as prophylaxis for SBP decreases HRS to 28% compared to 41%

Albumin administration at diagnosis and day 3 in patients with SBP decreases HRS. (10%)

Pentoxyphylline 400mg tid for 28 days in alcoholic hepatitis decreases HRS.( 24%)

However these are not proved in recent studies

prognosis

• Worst prognosis of all complications of cirrhosis.• Type 1 HRS without Rx < 2 weeks• All pts in 8-10 weeks after onset of RF.• Type 2 HRS - 6 months .

Lancet 2003 ;362:1819-1827

Unanswered questions….

• 1.best modality of therapy• 2.predictability of LKT versus a liver only transplant.• 3.how are vasoconstrictors compare with TIPS,MARS• 4.best to use vasoconstrictor?• 5.whether there is an independent beneficial effect of

albumin in HRS?• 6.why renal recovery rate is variable between centers.

TRIALSFabrizi F et al – meta analysis (2007) of terlipressin therapy for

HRS Sanyal A,boyer T,Teuber P(2007)-Randomised double blind

placebo controlled trail for terlipressin therapyIn both the trials showed that terlipressin is more effective than

placebo in reversing HRSNakaeh,Igarashi T,Tajimi K et al-case report of hepatorenal

syndrome treatment with plasma differentiation(2007)Rimola A,Navasa M,Grande et al-liver transplantation for

cirrhosis and ascitis(2005)

Take home message• 1.HRS is a functional reversible renal

failure in cirrhotic, fulminant liver failure patients.

• 2. patients with SBP ,who underwent LVP , had GI hemorrhage should be carefully followed up as they are more prone for HRS.

• 3 .diagnosis by exclusion ,based on major criteria.

• 4.type I HRS has high mortality ,HRS 2 prolonged survival ,type3 in CKD ,type 4 HRS - fulminant hepatic failure.

• 5.ppting factors identified in type I HRS ,refractory ascites assosciated with type 2 HRS.

• 6.TERLIPRESSIN is effective drug in phramacological therapy..

• 7.MARS is an upcoming procedure.• 8.Liver TRx is treatment of choice .• 9.MELD score does not work out

for HRS patients• 10.recovery depends on age,s

bilirubin,non alcoholic liver disease.• 11.role of LKT in patients with HRS

to be checked out.• 12.albumin infusion in patients with

SBP at 1.5 g/kg at admission,1 g/kg 48 hrs later prevents HRS,pentoxyfilline in alcoholic hepatitis.

REFERENCES

• MEDICINE UPDATE ,vol 17 , 2007 • HEPATORENAL

syndrome :pathophysiology and management :Amercian Society Of Nephrology ,2006

• Emedicine .com• Clinics of North America ,2006,2007 – care

of cirrhotic patients ,hepatic emergencies in cirrhosis.

• Mayoclinic.com• HARRISON’S PRINCIPLES OF INTERNAL

MEDICINE ,18th ed• World journal of

gastroenterology ,2007:4046-4055,

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