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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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Page 1: Cirrhosis by Dr. Matt Deneke

Cirrhosis: clinical pearls for the practicing internist

ADR / Jun 2013

Matt Deneke

10/20/2014

Page 2: Cirrhosis by Dr. Matt Deneke

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

Page 3: Cirrhosis by Dr. Matt Deneke

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

Page 4: Cirrhosis by Dr. Matt Deneke

General concepts about cirrhosis

ADR / Jun 2013

• Cirrhosis is the end result of chronic damage to the liver

Page 5: Cirrhosis by Dr. Matt Deneke

General concepts about cirrhosis

ADR / Jun 2013

• Cirrhosis is the end result of chronic damage to the liver

Altamirano. Ann Hepatol 2012;11:426

Page 6: Cirrhosis by Dr. Matt Deneke

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

Page 7: Cirrhosis by Dr. Matt Deneke

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%

Page 8: Cirrhosis by Dr. Matt Deneke

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

Page 9: Cirrhosis by Dr. Matt Deneke

Do I need a liver biopsy to diagnose cirrhosis?

ADR / Jun 2013

• Muehrckes’s and Terry’s nails

Page 10: Cirrhosis by Dr. Matt Deneke

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?

Page 11: Cirrhosis by Dr. Matt Deneke

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

Page 12: Cirrhosis by Dr. Matt Deneke

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

Page 13: Cirrhosis by Dr. Matt Deneke

Do I need a liver biopsy to diagnose cirrhosis?

ADR / Jun 2013

• Noninvasive markers of fibrosis: transient elastography– Fibroscan®

Page 14: Cirrhosis by Dr. Matt Deneke

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

Page 15: Cirrhosis by Dr. Matt Deneke

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

Page 16: Cirrhosis by Dr. Matt Deneke

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

Page 17: Cirrhosis by Dr. Matt Deneke

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

Page 18: Cirrhosis by Dr. Matt Deneke

Pros and cons of TIPS

ADR / Jun 2013

• TIPS: tranjugular intrahepatic portosystemic shunts

Page 19: Cirrhosis by Dr. Matt Deneke

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

Page 20: Cirrhosis by Dr. Matt Deneke

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

Page 21: Cirrhosis by Dr. Matt Deneke

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)

Page 22: Cirrhosis by Dr. Matt Deneke

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

Page 23: Cirrhosis by Dr. Matt Deneke

ADR / Jul 2012

Hepatorenal syndrome

• Hepatorenal syndrome– Definition

Francoz. J Hepatol 201052:605

Page 24: Cirrhosis by Dr. Matt Deneke

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

Page 25: Cirrhosis by Dr. Matt Deneke

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

Page 26: Cirrhosis by Dr. Matt Deneke

Pulmonary complications of cirrhosis

Page 27: Cirrhosis by Dr. Matt Deneke

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)

Page 28: Cirrhosis by Dr. Matt Deneke

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

Page 29: Cirrhosis by Dr. Matt Deneke

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

Page 30: Cirrhosis by Dr. Matt Deneke

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)

Page 31: Cirrhosis by Dr. Matt Deneke

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

Page 32: Cirrhosis by Dr. Matt Deneke

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

Page 33: Cirrhosis by Dr. Matt Deneke

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

Page 34: Cirrhosis by Dr. Matt Deneke

Hepatocellular Carcinoma

EASL HCC Guidelines, J Hepatol, 2012

Page 35: Cirrhosis by Dr. Matt Deneke

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

Page 36: Cirrhosis by Dr. Matt Deneke

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

Page 37: Cirrhosis by Dr. Matt Deneke

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)

Page 38: Cirrhosis by Dr. Matt Deneke

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

Page 39: Cirrhosis by Dr. Matt Deneke

ADR / Jul 2012

Internal Medicine in cirrhosis

• Pain treatment recommendations in cirrhosis:

Chandok. Mayo Clin Proceed 2010;85:451

Page 40: Cirrhosis by Dr. Matt Deneke

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

Page 41: Cirrhosis by Dr. Matt Deneke

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

Page 42: Cirrhosis by Dr. Matt Deneke

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

Page 43: Cirrhosis by Dr. Matt Deneke

Internal Medicine in cirrhosis

ADR / Jun 2013 Jalan. J Hepatol 2012;57:1336

Page 44: Cirrhosis by Dr. Matt Deneke

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

Page 45: Cirrhosis by Dr. Matt Deneke

Thanks…

ADR / Jun 2013


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