Cirrhosis: Management of Speakers Bureau/Honoraria : None Key - - PDF document

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Cirrhosis: Management of Key Complications – Part 2

Hemant Shah MD MScCH HPTE

Twitter: @hepatoMD

Jordan Feld MD MPH

Conflict of Interest Disclosure

• Dr. Shah
• Speakers Bureau/Honoraria: None
• Consulting Fees: Abbvie, Gilead, Merck, Intercept, Lupin, Bristol-

Myers Squibb

• Dr. Feld
• Research: Abbvie, Gilead, Janssen, Merck
• Consulting: Abbvie, Contravir, Enanta, Gilead

Key Learning Objectives

After this presentation, you may be able to:

• Update your knowledge on management of major

complications of cirrhosis

• Recognize opportunities for screening to prevent

complications

• Appreciate management strategies when complications arise

Complications of Cirrhosis Stages of Cirrhosis

D’Amico Gastro

Very useful for prognostication

Stages of Cirrhosis

1 year transition rates

Cirrhosis Stage 1 yr 5 yr

• 1. Compensated

99% 85%

• 2. +varices

96.5% 72%

• 3. +bleed

85% 78%

• 4. +ascites

74% 46%

• 5. +ascites+bleed

70% 33% HCC 55% Encephalopathy 53% Jaundice 58%

G D’Amico, G Garcia-Tsao, L Pagliaro. J Hepatol 2006;44(1):217 A20: G D’Amico et al. AASLD 2010

Death

30 26 15 3.5 1 22 8 5

Platelets INR Albumin Bilirubin

Hepatoma

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Issues in Cirrhosis Management

• Ascites
• SBP Prophylaxis
• Varices
• Encephalopathy
• Hepatocellular Cancer
• Others

Ascites Management of Ascites

1) Salt restriction - (66 mmol/d – 1.5-2 g/d) 2) Salt restriction – dietitian available – EatRight Ontario 3) Salt restriction! 4) Avoid Doctors -- NSAIDs, surgery, saline 5) Diuretics 6) Fluid restriction – only once hyponatremic 7) Paracentesis 8) TIPS 9) Transplant - All patients should be evaluated

Sodium Balance

Intake Output 100-150 mmol/d Typical No Added Salt Diet <20 mmol/d Typical Urinary Na+ Excretion of ascitic Pt on no diuretics

Result? Daily positive Na+ Balance

• f 80-130 mmol/d = 600-1000ml fluid/d

Diuretics

• International Ascites Club
• Recommend combo therapy:

Spironolactone 100 mg/d + Furosemide 40 mg/d

• With stepwise increase to max 400 + 160mg/d
• Check lytes/creat with every change
• If issues with gynecomastia – change spironolactone

to amiloride (10 mg = 100 mg)

Aim = 0.3-0.5 kg/d (1lb/d) without edema 0.8-1 kg/d (2lb/d) w/ edema

Urine electrolytes

• Useful if refractory ascites despite ‘adhering’ to low salt diet or on

lots of diuretics

• Goal is to measure sodium output, and then compare to sodium

input

• Two ways to measure:
• Spot Urine:
• Sodium-potassium ratio >1 is 90% predictive of Na excretion greater than

78mmol/d

• 24hr Urine:
• If done correctly, accurate sodium-excretion

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Interpreting Urine Sodium

If ascites difficult to manage (high-dose diuretics) and: Low urine sodium  Sodium-retainer, stop diuretics, may need paracentesis Moderate-High urine sodium  Sodium-excreter, consuming too much sodium, work on diet

Refractory Ascites

• Occurs 5-10% of patients with ascites
• Definition:

No response to Spironolactone 400 mg + Furosemide 160 mg/d or diuretic intolerance

• Check compliance
• if excreting > 78 mmol/d and gaining wt  CHEATING!
• Rule out other causes -- tumor, PV thrombosis etc

Bad Prognosis

Gines NEJM 2004

Worse than almost any cancer!

Options in Refractory Patients

1. Repeated large volume paracentesis + albumin 2. TIPS 3. Peritonvenous shunt

• Abandoned due to high complications

Gines NEJM 1991

Large volume taps

• Effective but high rate of recurrence
• Patients often prefer paracentesis to diet + diuretics
• Complications of protein/complement loss, infection

etc  prove diuretic resistant!!

• Replace albumin if >5L removed
• If require > 8L q 2 weeks -- non-compliant
• Low risk of SBP if no symptoms, therefore cell count,

but cultures not necessa

Spontaneous Bacterial Peritonitis - SBP

• Key is remember to check!
• 50% have no symptoms – no fever, no pain
• Rule: If someone with ascites presents to medical attention for

ANY reason…they need a tap to r/o SBP

• This is VERY poorly done at ALL hospitals
• Can be literally life-saving
• Cell count (neutrophils>250 or WBC>500) + culture in blood culture bottles
• After an episode of SBP – long-term prophylaxis
• Norfloxacin 400 mg daily or
• Ciprofloxacin 750 mg once per week

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Albumin and SBP

• Excellent evidence that giving high-dose albumin in

setting of SBP decreases mortality (19% @ 3 months)

• Dose:
• 1.5mg/kg on day 1
• 1 mg/kg on day 3
• A lot of albumin!
• For 70kg person, that’s 7 bottles of 25% albumin

Sort et al. NEJM. 1999; 341:403-409.

Varices Variceal screening

• Guidelines recommend every 2-3 years once cirrhosis diagnosed
• Not required if primary disease taken away e.g. HCV after SVR – no

need for endoscopy if no varices prior to SVR

• Once present – may consider increasing to annual surveillance
• If being selective:
• Fibroscan< 20 Kpa AND Platelets > 150  very low risk of varices that

require treatment and can forego endoscopy

Beta blockers vs Banding for Primary Prophylaxis

• Multiple trials - both better than placebo
• Mostly methodologically flawed (often significantly)
• Generally show a small benefit of banding over beta

blockers for patients with big varices (grade 3 or 4)

• Guidelines still suggest beta blockers – cost + safety
• If beta blockers not tolerated or very big varices 

band first

• Once on a beta blocker  no need to keep scoping!
• Aim for HR<60 bpm

When they do Bleed - Managing Varices

• Banding superior to beta blockers – repeat sessions q 4 weeks until

eradicated

• TIPS is an effective rescue therapy for bleeding
• Methods:
• Group 1: EBL + Medical Mgt w TIPS as rescue
• Group 2: Diagnostic Endo + TIPS w/in 72hrs
• e-PTFE-covered stents (dilated to 8 mm)
• If portal-pressure gradient >12 mmHg  stent dilated to 10

mm

• Primary Endpoint: Failure to control bleeding or re-bleeding within 1

year

Garcia-Pagan et al. 2010

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A clear benefit for early TIPS

Variceal bleed randomized to early TIPS (<72 h) vs standard care after octreotide + banding

• Very strong effect on rebleeding and survival
• Under-utilized in Toronto!

Garica-Pagan NEJM 2010 61% 86%

12 MONTHS ARR=25%; NNT=4.0 (CI 2.1-50.0) 42 DAYS ARR=30%; NNT=3.3 CI 2.1-8.3)

97% 67%

Encephalopathy Encephalopathy

• ‘Brain fog’ from liver disease
• Liver clears nitrogenous waste
• With shunting – waste products to the brain
• Mild to severe symptoms
• Asterixis – rarely focal neuro deficits, Parkinsonism
• Treatment:
• Avoid precipitants – meds, infection, bleeding
• Lactulose
• Laxative – changes rectal pH to change bacterial flora to decrease

ammonia producing bugs

• Others may work – recent study with PEG – I’m skeptical
• Rifaxamin
• Non-absorbable antibiotic – similar effect, no diarrhea
• Now covered by ODB (LU code)
• Driving…you don’t want them on the road…

Bass et al. NEJM. 2010; 326: 1071-1081.

Primary Outcome – Breakthrough First HE

Hazard Ratio 0.42, p<0,001

Other Issues for Cirrhotics

• Hepatocellular cancer screening
• US q 6months
• AFP recommendation back to equivocal
• Caveats: High if active hepatitis, often low in small HCCs – limits

sensitivity and specificity but still may be useful

• Particularly: Post-SVR for HCV, if you don’t trust your ultrasound!
• Vaccinations – ALL (remember annual flu)
• Infections
• low threshold to treat…sepsis is VERY common cause of

death…renal function very tenuous

• Findings may be subtle (normal WBC but high for cirrhosis)
• Statins and Anticoagulation - Emerging

Summary

• Main complications:
• Ascites
• Salt restriction, diuretics, screen for SBP!
• Varices
• Can avoid screening if FS<20 & Plt>150
• Encephalopathy
• Reverse ppt, lactulose, rifaximin, driving
• Cancer
• Surveillance with US +/- AFP
• Screen for problems and try not to precipitate them!