Download - Cirrhosis by Dr. Matt Deneke
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Cirrhosis: clinical pearls for the practicing internist
ADR / Jun 2013
Matt Deneke
10/20/2014
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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General concepts about cirrhosis
ADR / Jun 2013
• Cirrhosis is the end result of chronic damage to the liver
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General concepts about cirrhosis
ADR / Jun 2013
• Cirrhosis is the end result of chronic damage to the liver
Altamirano. Ann Hepatol 2012;11:426
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General concepts about cirrhosis
ADR / Sep 2012
Hepatic Stellate Cell Activation
Mild Fibrosis (F1)
Clinically Relevant Fibrosis (F2)
Cirrhosis (F4)
Advanced Fibrosis(F3)
Liver Insult (chronic)
Altamirano. Ann Hepatol 2012;11:426
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Jun 2013
• There are other methods for diagnosing cirrhosis:– Clinical manifestations– Previous manifestations of portal hypertension– Routine biochemical parameters– Non invasive markers of cirrhosis: Fibrotest® and Fibroscan®
Do not forget that there is:
Pain in 80%, bleeding 3%; need for transfusion, pneumothorax, perforation of hollow viscous, death in <1%
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Jun 2013
• Clinical manifestations of cirrhosis
Heidelbaugh. Am Fam Physician 2006;74:756
AB wall vascular collaterals Splenomegaly
Ascites Temporal atrophy (sarcopenia)
Asterixis Testicular atrophy
Fetor hepaticus
Gynecomastia Other more cause-specific
Hepatomegaly Clubbing, hypertrophic osteoarthropathy
Jaundice Dupuytren
Nail changes: Muehrcke’s / Terry’s Kayser-Fleischer ring
Palmar erythema Parotid hypertrophy
Scleral icterus P2 increased
Vascular spiders
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Jun 2013
• Muehrckes’s and Terry’s nails
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Feb 2013
• Previous manifestations of portal hypertension– How do we define portal hypertension? What is HVPG?
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Feb 2013
• Previous manifestations of portal hypertension– HVPG
Bosch. Nat Rev Gastroenterol Hepatol 2009;6:573
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Jun 2013
• Previous manifestations of portal hypertension
Varices / variceal bleeding
Ascites, hepatic hydrothorax
Hyponatremia
Hepatic encephalopathy
SBP / SB Empyema
Hepatorenal syndrome
Portopulmonary hypertension
Hepatopulmonary syndrome
Portal vein thrombosis
Hepatocarcinoma
Cirrhotic cardiomyopathy
Other
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Jun 2013
• Noninvasive markers of fibrosis: transient elastography– Fibroscan®
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Oct 2012Castera. J Hepatol 2008;48:835
• Noninvasive markers of fibrosis: transient elastography– Vibrating probe with low frequency and amplitude– Mounted to an ultrasound transducer (3.5 MHz)
Total volume measured ≈3 cm3
100 times the area of liver biopsy
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Do I need a liver biopsy to diagnose cirrhosis?
ADR / Oct 2012Castera. J Hepatol 2008;48:835
• Output: elastogram– Mathematic representation of propagation velocities– Limits 2.5 to 75 kPa
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Do I need a liver biopsy to diagnose cirrhosis?
Mariappan et al. Clin Anat. Jul 2010; 23(5): 497–511
• Elastography can also be performed using MRI
• Sensitivity and specificity for detecting the presence of fibrosis are 98 and 99% using a cutoff of 2.93 kPa
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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Pros and cons of TIPS
ADR / Jun 2013
• TIPS: tranjugular intrahepatic portosystemic shunts
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Pros and cons of TIPS
ADR / Jun 2013
• When to use a TIPS?
Boyer. Hepatology 2010;51:1
García-Pagán. N Engl J Med 2011;362:2370
Indications for TIPSEndoscopy refractory acute variceal bleeding
Acute variceal bleeding (CTP 7-13, after EGD)
Refractory ascites
Refractory hepatic hydrothorax
Hepatorenal syndrome (HRS type 2)
HRS type 1, after response to vasoconstrictors
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Pros and cons of TIPS
ADR / Jun 2013
• Hepatic encephalopathy: the Achilles heel of TIPS
Author Indication FU PSE-TIPS PSE-Ctrl Severity
Gines 2002 RefAsc 10 mo 27 (77%) 23 (66%) TIPS > Ctrl
Sanyal 2003 RefAsc 17 mo 22 (42%) 13 (23%) TIPS > Ctrl
Salerno 2004 RefAsc 18 mo 20 (61%) 13 (39%) TIPS > Ctrl
Narahara 2011 RefAsc 27 mo 20 (66%) 5 (17%)* -----
Garcia-Pagan 2010 VB 16 mo (10%) (19%) -----
Exclusion criteria (RefAsc):- Age >70-75 yo, PSE > grade 1, TB >3-10 mg/dL, Cr >1.5-3.0 mg/dL, INR >2-2.5, CTP >11
OR: 2.26 (IC95%: 1.35-3.76)Relative increased risk (MA)
D´Amico. Gastroenterol 2005;129:1282
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Pros and cons of TIPS
ADR / Jun 2013
• When not to use a TIPS (nor for acute bleeding)?
Contraindications Increased PSE RiskUncontrolled PSE Age >65
CTP ≥12 CTP ≥10
MELD ≥20 MELD ≥15
Bilirubin >5 mg/dL Bilirubin >3 mg/dL
Pulmonary HTN (>35 mmHg) Cr >1.3 mg/dL
Congestive HF Previous PSE
Hepatocarcinoma MAP <80 mmHg
Polycystic liver disease AbNL psychometric tests
Biliary obstruction Hyponatremia
Active infection Use of bare stents
INR >5 / Platelets <20,000 HVPG <12 mmHg (↓ 5 mmHg)
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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ADR / Jul 2012
Hepatorenal syndrome
• Hepatorenal syndrome– Definition
Francoz. J Hepatol 201052:605
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ADR / Jul 2012
HRS algorithm
• Hepatorenal syndrome: treatment (up to 14 days)– Terlipressin = Norepinephrine > Midodrine
Stop diureticsStop nephrotoxics
Stop NSbB?
Albumin 1 g/kg(≤100 g/d), then,
25-50 mg/d
Check:Urine sedimentUrine sodium
ProteinuriaRenal US
Midodrine 7.5 mg tid(↑ to 12.5 tid) +
octreotide 100 mcg tid (↑ to 200 tid)
Transfer to ICUNorepinephrine
0.05-0.1 mcg/kg/min (↑ 0.05
mcg/kg/min)
Monitor:Daily SBP
CVP (10-15)UO (Foley’s)
Ischemia
How to adjust vasopressors:CVP: >15, albumin 20 mg/d; >18, stop albumin + furosemide IV bolusMAP ↑ <10 mmHg or UO <200 mL (4 h): ↑ NE; Cr ↓ <25% (72 h): ↑ NE/midodrine
No response
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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Pulmonary complications of cirrhosis
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Pulmonary complications of cirrhosis
• Hepatopulmonary syndrome (HPS)– Effective shunting of
blood from pulmonary arteries to veins without oxygenation
• Capillary dilation• Collateral bypass channels• Hyperdynamic flow
J Gastro Hepatol 2013, 28(2)
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Pulmonary complications of cirrhosis
• Portopulmonary Hypertension– Identical to primary pulmonary HTN in appearance
and behavior– Reversible with liver transplantation if arterial
hypertrophy and fibrosis have not developed
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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Hepatocellular Carcinoma
• Hepatic malignancies are the sixth most common cancer worldwide– The vast majority are hepatocellular carcinoma
• Over 90% of patients with HCC have cirrhosis• The risk of developing HCC in patients with cirrhosis varies
– Five-year risk varies from 4-30%– Risk varies with etiology of cirrhosis
• Higher in HBV and HCV– Annual risk from 1% to 8% in HCV cirrhosis
• Higher with multifactorial liver disease (e.g. HCV + EtOH)
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Hepatocellular Carcinoma
• Prognosis for HCC is poor without definitive therapy• Surgical resection is ideal, but usually not an option for
patients with cirrhosis– Significant risk of decompensation– Significant risk of recurrent disease
• Liver transplantation is ideal therapy in cirrhosis, but only for selected patients – Early studies of patients transplanted with advanced HCC showed 5-
year survival of only 25% • Due to high risk of tumor recurrence
– For patients within Milan criteria, 5-year survival is excellent (>70%)• Similar to survival with nonmalignant indications
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Hepatocellular Carcinoma
• Milan Criteria– single lesion less than 5 cm– up to 3 lesions all less than 3 cm– no macrovascular invasion– no extrahepatic spread
www.medscape.com
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Hepatocellular Carcinoma
• Milan criteria require identification of HCC at an early stage• In order to accomplish this, screening of patients with
cirrhosis has been recommended– AASLD and EASL:
• Cross-sectional imaging with U/S every 6 months• Routine use of AFP is no longer recommended due to poor sensitivity and
specificity
• If lesion identified on screening, then contrast-enhanced CT or MRI along with AFP should be obtained– Diagnosis can be made without biopsy if typical imaging characteristics
are present or if AFP is very elevated
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Hepatocellular Carcinoma
EASL HCC Guidelines, J Hepatol, 2012
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Hepatocellular Carcinoma
• Treatment options for HCC not amenable to resection/OLT– Locoregional therapy
• Direct tumor ablation– Ethanol injection– Radiofrequency ablation– Very effective in small tumors
• Transarterial chemoembolization (TACE)– Often used in patients listed for transplant– Carries risk of causing hepatic decompensation
• Transarterial radioembolization (TARE, TheraSphere)– Used in large tumors or multifocal tumors
• Have been shown to prolong survival compared with no treatment
– Systemic therapy• Typical cytotoxic chemotherapy is not effective in HCC• Sorafenib is the only indicated agent for systemic therapy
– Prolongs survival by 3 months vs placebo– Tolerability is an issue– Patients with poor functional status usually do not tolerate it well
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute on chronic liver failure
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Internal Medicine in cirrhosis
ADR / Jun 2013
• Presurgical evaluation– http://www.mayoclinic.org/meld/mayomodel9.html– Or Google search for “Mayo Clinic cirrhosis surgical risk”
• Use of common drugs in cirrhosis– Metformin and sulfonylureas
• Stop when patient reaches CTP B (8 points) switch to insulin
– Statins• Cirrhosis is NOT a contraindication to statin use• Some studies suggest statins may reduce rate of progression of disease
and reduce risk of HCC (Kumar et al, Dig Dis Sci, Aug 2014; El-Serag et al, Gastroenterology, May 2009)
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Internal Medicine in cirrhosis
ADR / Jun 2013
• Never trust an HbA1c in advanced cirrhosis! – Anemia will decrease its predictive value
• Limit use of benzodiazepines– Favor propofol. If neuromuscular blockage cisatracurium
• Cirrhotics still have an increased risk for thromboembolism– Especially in those <45 year-old
• Hepatoadrenal syndrome (relative adrenal insufficiency)– Present in 33% of ALF and 65% of chronic liver disease and sepsis
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ADR / Jul 2012
Internal Medicine in cirrhosis
• Pain treatment recommendations in cirrhosis:
Chandok. Mayo Clin Proceed 2010;85:451
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ADR / Jul 2012
Internal Medicine in Cirrhosis
• Beware of Na in IV fluids & volume expansion with albumin
Osm mOsm/L
Na/Clmmol/L
Cl/K/Ca Max. Vol. Exp. (%)
Duration of Exp. (h)
Side Effects
NS 308 154/154 -/-/- 20-25 1-4 ↑ Cl
Ringer’s 275 130/110 4/3/28 20-25 1-4 ↑ K
DW5* 260 -/-/- -/-/- 20-25 <1-2 Edema
NS + DW5* 264 154/154 -/-/- 20-25 1-4 ↑Cl, edema
Albumin 5% 290 36/36# -/-/- 70-100 12-24 AllergyInfection
Albumin 25% 310 15/15$ -/-/- 300-500 12-24
*DW5 has 50 g of glucose = 200 kCal#In 250 mL; $in 100 mL
Rivers. Curr Opin Crit Care 2010;16:297
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Objectives
ADR / Jun 2013
• General concepts about cirrhosis• Natural history of cirrhosis• Pros and cons of TIPS• HRS treatment algorithm• Pulmonary complications of cirrhosis• Hepatocellular carcinoma• Internal medicine and cirrhosis: miscellaneous• The cirrhotic in the ICU
– Acute-on chronic liver failure
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Acute-on chronic liver failure (ACLF)
ADR / Jun 2013
• Acute deterioration of liver function in cirrhosis, either secondary to superimposed liver injury or due to extrahepatic precipitating factors such as infection, culminating in end-organ dysfunction
• Mortality 50-90% (single OF is reversible in 50% of cases)
Jalan. J Hepatol 2012;57:1336
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Internal Medicine in cirrhosis
ADR / Jun 2013 Jalan. J Hepatol 2012;57:1336
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Internal Medicine in cirrhosis
ADR / Jun 2013
• Mortality is defined by:– Degree of previous liver dysfunction & organ failure– It is difficult to estimate reversibility: immune paralysis?
Jalan. J Hepatol 2012;57:1336
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Thanks…
ADR / Jun 2013