Management of Decompensated Liver Disease

NBIMU 2019

Robert Berger MD FRCPC

X Medical Expert (as Medical Experts, physicians integrate all of the CanMEDS Roles, applying

medical knowledge, clinical skills, and professional values in their provision of high-quality and

safe patient-centered care. Medical Expert is the central physician Role in the CanMEDS

Framework and defines the physician’s clinical scope of practice.)

Communicator (as Communicators, physicians form relationships with patients and their

families that facilitate the gathering and sharing of essential information for effective health

care.)

X Collaborator (as Collaborators, physicians work effectively with other health care professionals

to provide safe, high-quality, patient-centred care.)

X Leader (as Leaders, physicians engage with others to contribute to a vision of a high-quality

health care system and take responsibility for the delivery of excellent patient care through their

activities as clinicians, administrators, scholars, or teachers.)

Health Advocate (as Health Advocates, physicians contribute their expertise and influence as

they work with communities or patient populations to improve health. They work with those they

serve to determine and understand needs, speak on behalf of others when required, and

support the mobilization of resources to effect change.)

X Scholar (as Scholars, physicians demonstrate a lifelong commitment to excellence in practice

through continuous learning and by teaching others, evaluating evidence, and contributing to

scholarship.)

Professional (as Professionals, physicians are committed to the health and well-being of

individual patients and society through ethical practice, high personal standards of

behaviour, accountability to the profession and society, physician-led regulation, and

maintenance of personal health.)

CanMEDS Roles Covered

Conflict of Interest Disclosure (over the past 24 months)

Commercial or Non-Profit

Interest Relationship

Medtronic Speakers panel, participating site for an RCT

Abbvie Speakers panel, Advisory Board

Janssen Speakers panel, Advisory Board

Takeda Advisory Board

Objectives

• Define decompensated liver disease

• Review the presentation of decompensated liver disease

• Discuss management of GI bleeding due to portal hypertension

• Review the causes and management of hepatic encephalopathy (HE)

• Develop an approach to ascites

Cirrhosis

Compensated Decompensated

- Ascites - Variceal hemorrhage - Hepatic Encephalopathy

Median survival 12 years Median survival 1.8 years

Prognosis in chronic liver disease

• Child-Turcotte-Pugh (A-C) • Ascites

• Albumin

• Bilirubin

• INR

• HE

• MELD Na score

Case 1

• A 60yo man with EtOH-related cirrhosis presents with 3 episodes of hematemesis

• HR 100 BP 91/58

• Hgb 87, Plt 72

• Na 132, Cr 96

• Bili 45, Albumin 30, INR 1.73

Case 1

• What is the differential diagnosis?

• What is the initial management?

• What is your target for BP?

• What is the appropriate Hgb target?

• What medications should be initiated?

• Upper GI bleeding in cirrhosis is not always secondary to esophageal/gastric varices

• Resuscitation • May require prophylactic intubation • IV fluids (colloid/crystalloid/blood products/clotting factors) • Be aware of the risk of over-resuscitating causing worsening portal HTN

• Should be admitted to a step-down unit or ICU

• Initial medical management • PPI • Octreotide (50mcg bolus then 50mcg/hr gtt)

• Call GI?

7fg4e

Abraldes et al. World J Gastroenterol 2006.

• 921 patients randomized to liberal (90) or restrictive (70) transfusion strategy

• Excluded patients with Rockall score of 0, Hgb >120 or exsanguination

• 50% were due to PUD

• Primary outcome was mortality at 45 days

PRBC transfusion can be detrimental in acute GI bleeding in patients with portal HTN • A restrictive transfusion strategy (target Hgb 70-80) is an appropriate

target in most patients and has been associated with improved survival

Villanueva et al. NEJM 2013.

Antibiotics are essential in acute GI bleeding in cirrhosis with portal HTN • Infection is a common cause of

morbidity and mortality in this setting

• 20% of patients have an infection on presentation and 50% will develop one during the hospitalization

• Prophylactic antibiotics in this setting have been shown to improve survival

Medical therapy - Antibiotics

Chavez-Tapia et al. Aliment Pharmacol Ther 2011

Case 2

• A 55yo man with NASH-related cirrhosis presents with decreased LOC

• No recent GI bleeding or trauma

• No new medications

• PMHx: HTN, dyslipidemia, DM2

• Home meds: • Lasix 40mg od

• Coversyl 4mg od

• Crestor 10mg od

• Metformin 500mg bid

• On exam, he is slow to answer questions and not oriented to time

• +asterixis, +ascites

• CT head negative

• Labs • ALT 42, AST 45, ALP 100

• Bili 58, Albumin 30, INR 1.92

• WBC 7.3, Hgb 110, Plt 64

• Na 129, Cr 172

Case 2

• What issues need to be addressed?

• What is the cause of the decreased LOC?

• What further tests are needed?

• Do you need to correct the hyponatremia?

• What is the likely cause of AKI? What is the initial treatment?

Issues

• Decreased LOC: ?hepatic encephalopathy

• Advanced liver disease • CTP C (13)

• MELD Na = 29

• Acute kidney injury

• Hyponatremia

Altered LOC in setting of cirrhosis

• Hepatic encephalopathy • This is a clinical diagnosis

• A good physical examination is essential to diagnosing HE

Vilstrup et al. J Hepatol 2014.

Hepatic Encephalopathy (HE)

• Minimal • Abnormal psychometric testing

• Grade I • Cognitive/behavioral delay

• Grade II • Lethargy, asterixis, disoriented to time

• Grade III • Confused, somnolent, disoriented to space

• Grade IV • Coma

HE: Differential Diagnosis

• Rule out other causes of decreased LOC

• Precipitating factors: • Infections

• GI bleeding

• Medications • Diuretics, Opioids, BZDs, sleep aids

• Electrolyte abnormalities

• Constipation

HE Treatment

• Lactulose • 30-45mL tid-qid for a target of 2-3 soft BM/day

• Rifaximin • Use if persistent HE despite lactulose or intolerance

• Dosed at 550mg bid

• If not alert enough for po meds: • Lactulose enema: 300mL lactulose mixed with 700mL water or saline

Ascites

• 85% of ascites is secondary to cirrhosis with portal hypertension

• Most common decompensation in cirrhosis

• 15% mortality at 1 year

• Paracentesis helps determine the cause of ascites: • Serum-ascites albumin gradient (SAAG) >11 is consistent with portal

hypertension

• Presence of ascites is an important consideration in any patient presenting to hospital

Does the patient have ascites?

Williams et al. JAMA 1992. Ennis et al. Int J Clin Med 2014.

Spontaneous Bacterial Peritonitis (SBP)

• 10-30% of patients with ascites admitted to hospital develop spontaneous bacterial peritonitis (SBP)

• Mortality ranges from 15-30%

• Guidelines recommend all patients with ascites admitted to hospital have diagnostic paracentesis

• Early Paracentesis (EP) • Paracentesis done within 12 hours from the first documented physician

contact

• Delayed Paracentesis (DP) • Paracentesis performed 12-72 hours after first physician contact

Paracentesis should not be delayed

Kim et al. Am J Gastroenterol 2015.

• Fluid analysis: • Cell count and differential

• Gram stain, c&s

• >250 x 106 /L PMN

• For diagnostic paracentesis • 22g needle

• Bleeding risk <1/1000

• No need for platelets or coagulation factors

SBP Treatment

• Prompt initiation of antibiotics • Cefotaxime 2g IV q8h or similar 3rd generation cephalosporin

• Albumin • One trial showed a 19% decrease in mortality

• ?if elevated urea, Cr or bilirubin

• 1.5g/kg on day 1 and 1g/kg on day 3 • can be given as Albumin 25% 100cc bid for 3 days

Sort et al. NEJM 1999. Runyon et al. Hepatology 2012.

SBP Prevention

• If on a PPI, reassess PPI indication

• Abx prophylaxis in upper GI bleeding

• Secondary prophylaxis

• Ascites fluid protein <1.5g/dL with:

Long-term Management of Ascites

• Initiate a sodium-restricted diet to <2g/day

• Usual starting dose of diuretics • Spironolactone 100mg daily

• Lasix 40mg daily

HRS dx only made after IV fluids and r/o other causes • AKI in portal hypertension often IS NOT HRS

• Diagnosis: • Cirrhosis with ascites

• Serum Cr >133

• No improvement in Cr after 48hrs fluid resuscitation and discontinuation of diuretics

• No evidence of shock

• Absence of current or recent nephrotoxic agents

• Absence of parenchymal kidney disease

• Manage as AKI and rule out SBP

Medication considerations in decompensated cirrhosis

• ACEi and ARB • Adversely effects renal blood flow in portal HTN (particularly with ascites)

• Beta blockers • Can be detrimental in refractory ascites

• Metformin • Safe

• Statins • Safe

• NSAIDs • Avoid

• Acetaminophen • Safe in lower doses (up to 2g/day)

• Opioids/Benzodiazepines/Sleep aids • Be cautious

Summary

• Patients with cirrhosis presenting with GI bleeding require prophylactic antibiotics

• If hepatic encephalopathy is suspected, it will largely be determined by history and physical examination

• Spontaneous bacterial peritonitis is common in hospitalized patients and these patients should all have a diagnostic paracentesis

• AKI in the setting of cirrhosis is often not related to hepatorenal syndrome and this diagnosis should be reserved for patients where other causes have been ruled out and have been adequately fluid resuscitated

• A diagnosis of cirrhosis should prompt a review of the patient’s medications

Thank you!

• Questions?