Role of Nurse Practitioners

in the Management of
Cirrhotic Patients
Kristina Tuesday Werner, DNP, FNP-C, and Shari Terese Perez, MSN, ANP-C

ABSTRACT
Patients with end-stage liver disease (ESLD) often suffer from complications that
require ongoing management with outpatient providers. Complications include ascites,
hepatic encephalopathy, hyponatremia, pulmonary vascular complications, and
esophageal varices. Patients with cirrhosis need to be referred to a hepatologist to estab-
lish care and potential evaluation for liver transplantation. Nurse practitioners (NPs)
involved in the care of cirrhotic patients are well positioned to provide supportive care,
improve symptom management, and prevent complications associated with further
decompensation. This article discusses the role of NPs in the management of patients
with cirrhosis.

Keywords: ascites, cirrhosis, esophageal variceal rebleeding, hepatic encephalopathy,

hepatocellular carcinoma, portal hypertension
© 2012 American College of Nurse Practitioners

C irrhosis is the 12th leading cause of death in

the United States, with more than 27,000
deaths annually.1 The estimated prevalence of
cirrhosis, as identified by autopsy studies, ranges from
4.5% to 9.5% of the general population.2 The prevalence
are identified as being in a compensated or decompen-
sated state based on the degree of portal pressure and the
occurrence of clinical complications. A well-compensated
(minimal to no symptoms) cirrhotic patient has a 5-year
survival rate of 91%.2 Patients who develop decompensa-
of cirrhosis is difficult to ascertain because it is often tion with hepatic encephalopathy (HE), esophageal
clinically silent in progression until a decompensating variceal (EV) bleeding, or ascites have a decreased sur-
event occurs. Cirrhosis consists of fibrosis (deposition of vival rate of 50%.3
scar tissue or extracellular matrix of the liver) and nodu-
lar regeneration in response to chronic liver injury.1 DIAGNOSIS OF CIRRHOSIS
Fibrosis ultimately leads to cirrhosis as a result of hepato- While a liver biopsy is the gold standard for cirrhosis diag-
cytes undergoing chronic wound-healing cycles from a nosis, the procedure has its risks and benefits and is not
variety of insults. Globally, the most common causes of always necessary. Limiting factors associated with obtaining a
liver cirrhosis are thought to be from hepatitis B virus liver biopsy include procedural invasiveness and the fact that
(HBV), hepatitis C virus (HCV), and alcohol.2 biopsy samples represent only about 1/50,000 of the liver
Patients with end stage liver disease (ESLD) or cir- parenchyma, yielding chances of sampling error.4
rhosis are at risk for many potential complications. Portal In the past few years, a great deal of effort has been
hypertension (PH) is the earliest and the most important devoted to the development of noninvasive methods of
consequence of cirrhosis and underlies most of the clini- detecting significant fibrosis. Among them, the tran-
cal complications of the disease. PH results from an sient elastography (Fibroscan®) has been developed
increased intra-hepatic resistance combined with mainly to focus on patients with viral hepatitis because
increased portal and hepatic arterial blood flow.2 Patients they have significant prognostic and therapeutic impli-

816 The Journal for Nurse Practitioners - JNP Volume 8, Issue 10, November/December 2012
cations.4 Fibroscan is an apparatus consisting of a 5 The clinical spectrum of cirrhosis ranges from asymp-
MHz ultrasound transducer probe mounted on the tomatic liver disease to hepatic decompensation.1 The
axis of a vibrator. Amplitude and frequency vibrations complications of cirrhosis and its management will be dis-
are transmitted to the liver tissue to induce an elastic cussed, including ascites, hyponatremia, recurrent EV
shear wave and measure its speed, which is directly bleeding, pulmonary vascular complications, HE, HCC,
related to liver tissue stiffness.3 The main limitation of and the importance of immunizations in cirrhotic patients.
the device is that about 15%-20% of obese patients get
uninterpretable results.4,5 The diagnosis of cirrhosis is Ascites
made with high certainty based on the clinical symp- Ascites is the most common complication of ESLD, affect-
toms and radiologic results.1 Clinical manifestations ing approximately 10% of all cirrhotic patients.8 It is associ-
may include jaundice, spider angiomata, splenomegaly, ated with a 50% mortality in 5 years if the patient does not
ascites, HE, palmar erythema, gynecomastia, and scarce undergo LT.8 The presence of ascites not only affects qual-
pubic and axilla hair.6 ity of life but also predisposes the individual to the devel-
opment of various complications, which decreases survival.
MODEL FOR ESLD AND LIVER TRANSPLANTATION The pathogenesis of ascites in cirrhosis is a complex process
The presence of cirrhosis alone does not warrant the need initiated by PH, followed by splanchnic and systemic
for liver transplantation (LT) unless there are complications, vasodilation, leading to renal sodium and water retention.9
such as development of hepatocellular carcinoma (HCC), Medical management of ascites in cirrhosis consists of treat-
worsening PH, and hepatic synthetic dysfunction. The ing the underlying cause, avoiding neprotoxic agents,
Model of End Stage Liver Disease (MELD) score is based restricting sodium in the diet, and taking a stepwise
on objective values, including serum bilirubin, international approach to the use of diuretics.
normalized ratio (INR), and serum creatinine.6 The MELD Dietary sodium restriction. The mainstay of treat-
score has been proven to be an excellent predictor of mor- ment for ascites is dietary sodium restriction since fluid
tality in patients with cirrhosis and is associated with overload is the consequence of intense renal sodium and
increasing severity of hepatic dysfunction, as well as 3- water retention. Reducing ascites and edema requires
month mortality risk.7 The MELD score ranges from 6 to negative sodium balance and increasing urinary output.9
40 and the higher the score the higher the mortality. Educating the patient about the importance of dietary
Patients with MELD scores approaching 10 or presence of sodium restriction is the mainstay of management. It is
any complications should be considered for LT evaluation. recommended that the patient consume no more than 2
LT is the definitive and widely accepted therapy for grams of sodium per day.8 Dietary counseling may also
improving survival and quality of life compared to conser- reinforce dietary sodium restrictions and provide educa-
vative therapy for patients with ESLD or early HCC.2,6 tion on appropriate food choices for these patients
Thus, improvement in cirrhosis management increases the because this is a significant change in daily dietary pat-
chances of patient becoming an LT candidate. tern for many individuals.
Diuretic therapy. Diuretics increase renal sodium
THE NURSE PRACTITIONER ROLE IN PATIENT excretion by blocking sodium reabsorption along the
MANAGEMENT various nephron sites, followed by water excretion.9 The
The management of cirrhosis has improved over the past most successful therapeutic regimen is the combination
decade. Progress in the treatment of decompensating of distal tubule diuretic, such as spironolactone, and a
events such as variceal bleeding, spontaneous bacterial loop diuretic, such as furosemide. Initial doses should
peritonitis, HCC, and HE have led to significant begin with 100 mg and 40 mg, respectively.9 The maxi-
improvement in survival rates, reduction in hospitaliza- mum recommended daily dosing of these diuretics are
tions, and improvement of quality of life.7 Nurse practi- spironolactone 400 mg and furosemide 160 mg.9
tioners (NPs) who are involved in the management of Maintaining this dose ratio often sustains normokalemia
patients with cirrhosis are well positioned to provide sup- with single daily dosing for both drugs in the morning.
portive care, improve symptom management, and prevent Taking both diuretics together first thing in the morning
complications leading to decompensating events. maximizes compliance and avoids nocturia.9

www.npjournal.org The Journal for Nurse Practitioners - JNP 817

 The doses can be doubled if there is no clinical with a higher risk of developing hepatic encephalopa-
response, defined as ⬍ 1.5 kg weight loss in 1 week thy.11 The mechanism is likely changes in serum osmolal-
despite low sodium diet adherence and absence of renal ity that lead to astrolyte swelling.11 The evolving cellular
9
failure. Patients on diuretic therapy must be monitored edema produces a cellular release of solutes to prevent
regularly for electrolyte imbalance, overdiuresis, and renal fatal cerebral edema.11
failure. Diuretics should be reduced or discontinued if a The first step in hyponatremia management is to
patient develops orthostatic symptoms, confusion, exces- identify whether it is hypovolemic or hypervolemic. All
sive weight loss, or acute renal failure. diuretics must be stopped because they reduce sodium
Refractory ascites. serum levels. In hypovolemic
Refractory ascites is defined hyponatremia, it is necessary to
as persistent ascites with less identify and treat the cause of
than 1.5 kg weight loss per The first step in sodium loss together with
week despite daily doses of hyponatremia management sodium administration. The key
diuretics and patient adher- is to identify whether it is is to increase renal solute-free
ence with dietary sodium water excretion and normalize
10
restrictions. Patients who do
hypovolemic or total body water.
not respond or tolerate hypervolemic. Correcting hyponatremia
diuretics because of side before LT may reduce the risk
effects may respond to treat- of neurological complications
ments other than medical therapy, such as large vol- after transplantation.11 The available therapeutic methods
ume paracentesis or insertion of transjugular for correction include fluid sodium restriction (1,000-
intrahepatic portosystemic shunt (TIPS).10 Once 1,500 mL/day) and administration of intravenous hyper-
refractory ascites develops, the prognosis is decreased, tonic sodium chloride and albumin.11 The use of
and these patients should be considered for LT. selective vasopressin antagonists can be considered if
other methods fail.11 In the United States, tolvaptan is
Hyponatremia approved for patients with cirrhosis with serum level ⱕ
Patients with cirrhosis and ascites frequently develop an 125 mEq/L.
impaired kidney capacity to eliminate solute-free
water.11 Hyponatremia in some cirrhotic patients may Recurrent Variceal Bleeding
be moderate, and usually these patients are able to nor- Esophageal varices are present in 25%-40% of patients
mally eliminate water and maintain a normal sodium with cirrhosis.12 The mortality rate from a single episode
level concentration. In other patients, the disorder is of bleeding 30 years ago exceeded 50% at 2 months.12
markedly severe, and they retain most of the water, However, with the advances in management, the mortality
causing hyponatremia and hypoosmolality. rate has dropped to 20%-30% at 6 weeks.12 The risk of
Hypervolemic hyponatremia, otherwise known as rebleeding is high within the first 2 weeks after a variceal
dilutional hyponatremia, is defined as a serum sodium bleed and gradually decreases during the next month if
concentration less than 130 mEq/L in the presence of treated appropriately with nonselective beta blockers and
ascites and edema.11 Hypervolemic hyponatremia has variceal band ligation.12
been indicated in 15% of cirrhotic individuals in the Screening esophagogastroduodenoscopy (EGD) to
first year of diagnosis and has only a 25% probability evaluate for EV should be done soon after the diagno-
of survival at 1 year.11 Recent studies indicated that sis of cirrhosis. Pharmacologic prophylaxis is usually
hyponatremia is an important marker of prognosis in not indicated for compensated patients with small
patients with cirrhosis awaiting LT and may be associ- varices, but EGD should be repeated every year.
ated with increased morbidity and reduced survival Patients with medium or large varices should be
after LT. 11 treated with nonselective beta blocker and prophylac-
In most patients, hyponatremia is asymptomatic; how- tic variceal band ligation.12 Decompensated patients
ever, recent data indicate that hyponatremia is associated should be treated with beta blockers because they are

818 The Journal for Nurse Practitioners - JNP Volume 8, Issue 10, November/December 2012
considered high risk for esophageal variceal bleed.12 evaluation. The presence of moderate to severe POPH
The standard of care for patients with history of significantly increases perioperative transplant mortality.14
variceal bleeding is a combination of nonselective beta The most common initial presentation in patients
blockers and surveillance with EGD. If portal hyper- with is dyspnea on exertion. Other common symptoms
tension is not controlled and rebleeding occurs, man- include fatigue, edema, light-headedness, and orthopnea.
agement by surgical portacaval shunts or TIPS Physical examination reveals elevated jugular vein pres-
procedure is recommended. sure, an accentuated pulmonic second heart sound, lower
extremity edema, and murmur consistent with tricuspid
Pulmonary Vascular Complications regurgitation.14 POPH is often diagnosed in patients
There are 2 common pulmonary complications of cir- with PH who are symptomatic, but it is not uncommon
rhosis: hepatopulmonary syndrome (HPS) and por- in asymptomatic patients, as symptoms of POPH are
topulmonary hypertension (POPH). The root cause often subtle and can be difficult to distinguish from
leading to such event is PH. The diagnosis for both symptoms as a result of PH.
conditions requires high level of suspicion, and outpa- Similar to HPS, clinical POPH features are often
tient assessment can lead to the diagnosis. LT cures nonspecific and require a high index of suspicion.
HPS, and a select group of patients with POPH may Transthoracic echocardiography is recommended for
benefit from it. screening, and right heart catheterization is required to
HPS is defined by widened, age-corrected, alveolar establish the diagnosis.14 The estimated right ventricu-
arterial oxygen gradient on room air with or without lar systolic pressure ⬎ 40-50 mmHg or presence of
hypoxemia resulting from intrapulmonary microvascular right ventricular abnormalities is a sensitive criterion
alterations or angiogenesis in the presence of liver dys- for POPH.14
function or PH.13 HPS is found in 15%-20% of cirrhotic There are no consensus treatment guidelines for
patients and its presence may increase mortality, especially POPH. A number of medical therapies have been suc-
if hypoxemia is present.13 Most of these patients have cessfully used, but supporting scientific evidence con-
mild to moderate oxygenation abnormalities (mild 46% sists primarily of case reports and retrospective
PaO2 ⬎ 80 mmHg, moderate 36% PaO2 60-80 mmHg, analysis. No controlled trials have been performed that
severe 18% PaO2 ⬍ 60mmHg); clinical features typically indicate whether such medical therapies improve sur-
involve respiratory complaints and findings associated vival in cirrhotic patients. The safety and efficacy of
with chronic liver disease.13 LT remains controversial.14
Platypnea (shortness of breath exacerbated by sitting
up and improved by lying down) and orthodeoxia Hepatic Encephalopathy
(hypoxemia exacerbated in the upright position) are HE is seen in 27% to 75% of all patients with cirrhosis,
classic symptoms as a result from gravitational increase depending on the diagnostic criteria, which can vary
in blood flow through dilated vessels in the lungs.13 and be subjective in nature.15 Although there are no
There are no reliable clinical predictors for HPS and no specific recommendations for routine treatment, early
established screening guidelines, but pulse oximetry- recognition and treatment have been the emphases of
based screening protocols are useful in identifying care. The main goal of management is to reverse the
hypoxemic patients and furthering the diagnosis. There episode of HE. The initial standardized strategy is to
are no available medical therapies, although LT is effec- look for the precipitating factors, concomitant causes of
tive in reversing HPS.13 HE, and initiate empirical treatment.15 An acute episode
POPH is defined by pulmonary vasoconstriction and of HE may be precipitated by sepsis, gastrointestinal
increased vascular resistance in the pulmonary vascular bleeding, constipation, dietary protein overload, dehy-
bed.14 Current diagnostic criteria include the presence of dration or electrolyte imbalance, use of sedatives, or
PH, mean pulmonary artery pressure ⬎ 25 mmHg at poor compliance with lactulose therapy. Concomitant
rest, pulmonary capillary wedge pressure ⬍ 15 mmHg, causes of HE include intracerebral hemorrhage,
and pulmonary vascular resistance ⬎ 240 dynes/s/cm5.14 hypoxia, hypercapnia, hypoglycemia, uremia, use of
POPH is found in 1%-8% of patients undergoing LT sedatives, acidosis or electrolyte imbalance, post ictal

www.npjournal.org The Journal for Nurse Practitioners - JNP 819

state, delirium tremens, or Wernicke encephalopathy. liver disease and cirrhosis. Streptococcus pneumoniae
Other situations that may lead to HE include large infections are more severe in patients with cirrhosis com-
spontaneous portosystemic shunts, post TIPS, diabetes pared to the general population. The 23-valence polysac-
mellitus, small bowel bacterial overgrowth, development charide vaccine is recommended by CDC for adults and
of HCC, the presence of glutaminase gene variant, and children 2 years and older. If patients are vaccinated
urea cycle disorders.15 before age 65, a booster dose is required if more than 5
Treatment of HE is initiated by lactulose 30 g twice a years have elapsed since the last dose.18 In contrast, a
day with titration of dose to 2 to 3 bowel movements booster dose is not needed if the first dose occurred at
per day.15 Second line of treatment is to add rifaximin 65 or older.18 In patients with cirrhosis, this vaccine is
550 mg by mouth twice daily, mainly to prevent recur- often given at time of diagnosis.
rent HE.15 Additional treatments such as neomycin,
metronidazole, and nitazoxanide have been used. CONCLUSION
Patients with cirrhosis are at high risk for many life-threat-
Hepatocellular Carcinoma ening complications that can often be managed or detected
HCC is the most common primary malignancy of the early in the outpatient setting. The role of the NP as an
liver and the primary cause of death in patients with agent for continuity of care and as a coordinator among
cirrhosis.16 The annual incidence of developing HCC multidisciplinary team members is vital to improve survival
is 1.4% in patients with compensated cirrhosis and 4% and quality of life. Once a patient is diagnosed with cirrho-
in patients with decompensated cirrhosis.16 HCC sis, the NP should refer him or her to a hepatologist for
screening (ultrasound, computed tomography, or mag- timely LT evaluation. It is important for the NP to make
netic resonance imaging) with testing of alphafetopro- sure that the patient with cirrhosis receives the necessary
tein every 6- 12 months is recommended in cirrhotic screening, medical management, and immunizations neces-
patients. Early detection and proper staging is the key sary to maintain optimal health.
step to appropriate treatment in cirrhotic patients
References
with HCC. Survival has improved as patients with
1. Dong MH, Saab S. Complications of cirrhosis. Dis Mon. 2008;54:445-456.
limited tumor burden may be eligible for potentially 2. Lim YS, Kim WR. The global impact of hepatic fibrosis and end-stage liver
curable treatment options, including surgical resection, disease. Clin Liver Dis. 2008;12:733-746, vii.
3. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient
ablation of HCC lesions with transarterial chemoem- elastography for the staging of liver fibrosis: a meta-analysis.
Gastroenterology. 2008;134:960-974.
bolization, radiofrequency or microwave technology, 4. Degos F, Perez P, Roche B, et al. Diagnostic accuracy of FibroScan and
or LT. comparison to liver fibrosis biomarkers in chronic viral hepatitis: a
multicenter prospective study (the FIBROSTIC study). J Hepatol.
2010;53:1013-1021.
5. Berzigotti A, Abraldes JG, Tandon P, et al. Ultrasonographic evaluation of
Immunizations liver surface and transient elastography in clinically doubtful cirrhosis. J
Superimposed infections of HAV or HBV in cirrhotic Hepatol. 2010;52:846-853.
6. Sirivatanauksorn Y, Dumronggittigule W, Limsrichamrern S, et al. Quality of
patients lead to higher morbidity and mortality.17 The life among liver transplantation patients. Transplant Proc. 2012;44:532-538.
7. Bambha KM, Biggins SW. Inequities of the Model for End-Stage Liver
timing of vaccine administration is important as patients Disease: an examination of current components and future additions. Curr
Opin Organ Transplant. 2008;13:227-233.
with compensated cirrhosis are noted to have better 8. Gines P, Cardenas A. The management of ascites and hyponatremia in
immunogenicity compared to patients with decompen- cirrhosis. Semin Liver Dis. 2008;28:43-58.
9. Runyon BA. Management of adult patients with ascites due to cirrhosis: an
sated cirrhosis.17 Immunizations to HAV and HBV are update. Hepatology. 2009;49:2087-2107.
10. Salerno F, Guevara M, Bernardi M, et al. Refractory ascites: pathogenesis,
safe and highly efficacious if given in patients with definition and therapy of a severe complication in patients with cirrhosis.
compensated cirrhosis. Liver Int. 2010;30:937-947.
11. Vaidya C, Ho W, Freda BJ. Management of hyponatremia: providing
Patients with compensated cirrhosis should receive treatment and avoiding harm. Cleve Clin J Med. 2011;77:715-726.
12. Khaderi S, Barnes D. Preventing a first episode of esophageal variceal
yearly influenza and pneumoccocal polysaccharide vac- hemorrhage. Cleve Clin J Med. 2008;75:235-244.
cines. Seasonal influenza infections have been shown to 13. Fallon MB, Krowka MJ, Brown RS, et al. Impact of hepatopulmonary
syndrome on quality of life and survival in liver transplant candidates.
increase liver decompensation and death in patients with Gastroenterology. 2008;135:1168-1175.
14. Kawut SM, Krowka MJ, Trotter JF, et al. Clinical risk factors for
cirrhosis.18 As recommended by the Centers for Disease portopulmonary hypertension. Hepatology. 2008;48:196-203.
Control and Prevention (CDC), annual influenza immu- 15. Bajaj JS, Wade JB, Sanyal AJ. Spectrum of neurocognitive impairment in
cirrhosis: implications for the assessment of hepatic encephalopathy.
nizations should be provided for patients with chronic Hepatology. 2009;50:2014-2021.

820 The Journal for Nurse Practitioners - JNP Volume 8, Issue 10, November/December 2012
16. Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and
treatment: the BCLC update and future prospects. Semin Liver Dis.
2010;30:61-74. 2013 NADNP Dermatology Conference
17. Kumar M, Herrera JL. Importance of hepatitis vaccination in patients with
chronic liver disease. South Med J. 2010;103:1223-1231.
18. Centers for Disease Control and Prevention. Recommended adult You asked
& we listened!

Save
immunization schedule—United States, 2011. MMWR 2011;60:1-4.
NEW AESTHETIC
WORKSHOP

Kristina Tuesday Werner, DNP, FNP-C, is a nurse practitioner

and instructor of medicine at Mayo Clinic in Phoenix, AZ, and the Date EXTENDED BIOPSY,
can be reached at [email protected]. Shari Terese NPs FROM ALL SURGERY, & WOUND CARE
DISCIPLINES WELCOME WORKSHOPS
Perez, MSN, ANP-C, is an adult nurse practitioner with
Transplant Hepatology at Mayo Clinic Hospital in Phoenix,
May 14-18, 2013
AZ. In compliance with national ethical guidelines, the authors
EXTENDED
report no relationships with business or industry that would pose DERMATOPATHOLOGY
& SKIN CANCER LECTURES
a conflict of interest.

1555-4155/$ see front matter

© 2012 American College of Nurse Practitioners
http://dx.doi.org/10.1016/j.nurpra.2012.08.016

To be held at the
Sheraton
Sand Key Resort
in CLEARWATER BEACH, FLORIDA
Rooms for $159 plus tax.
Book Now! These rooms sold out quickly
for the last conference!

Skin cancer treatments,

including cutting edge
melanoma updates
Wound care from
lymphedema to grafts
Biopsy and surgical procedures
Aesthetics and laser safety
Dermoscopy training
Dermatopathology
Basic and advanced
skin disease overviews
Pediatric dermatology
Leading the way GYN dermatology
in dermatology Professional development
for NPs... by NPs . . . and much more!

Fly via Tampa Airport

PLENTY OF ACTIVITIES FOR FRIENDS & FAMILY OF ATTENDEES

Register @ www.nadnp.net
EARLY BIRD REGISTRATION STARTING IN AUGUST.
DON’T DELAY, LAST YEAR’S CONFERENCE SOLD OUT!
EARLY BIRD SPECIAL! BOOK BY NOV.30 TO SAVE $50!
MEMBERS $300 NON-MEMBERS $365

www.npjournal.org The Journal for Nurse Practitioners - JNP 821