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36 The Nurse Practitioner • Vol. 40, No. 1 www.tnpj.com36 The Nurse Practitioner • Vol. 40, No. 11 www.tnpj.com
nonalcoholic
Treating the patient with
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.tnpj.com The Nurse Practitioner • November XXXXXXXXXX
onalcoholic fatty liver disease (NAFLD) covers a
wide spectrum of fatty liver issues, ranging from
simple fatty infi ltration in liver cells (hepatocytes)
to nonalcoholic steatohepatitis (NASH), to ci
hosis and
or hepatocellular carcinoma (HCC).1 With the increasing
prevalence of obesity, type 2 diabetes mellitus,
and metabolic syndrome, the prevalence of
NAFLD is also increasing, and NPs will be caring
for these patients more frequently.2 This
article seeks to improve the understanding
of the spectrum of NAFLD and provide
up-to-date treatment recommendations.
■ Background and prevalence of NAFLD
NAFLD is defi ned as biopsy- or imaging-proven hepatic
steatosis, in which other causes of fatty liver have been
excluded, including alcoholic liver disease, genetic diseases,
or medication-related causes.3,4 (See Defi nition of signifi cant
alcohol consumption.) NAFLD should be considered as a
diagnosis in patients who have had other causes of liver
disease excluded and who have one or more risk factors for
NAFLD (see Risk factors for development of NAFLD).
Ninety percent of patients with NAFLD have one or more
of the following risk factors: obesity, insulin resistance, met-
abolic syndrome, type 2 diabetes mellitus, cardiovascular
disease, hypertension, dyslipidemia, elevated triglyceride
levels, and/or low high-density lipoprotein levels.3-5
The prevalence of NAFLD is approximately 20% world-
wide and 25% in Western countries, making it one of
the most common causes of liver disease.2-4,6 NAFLD
occurs in one in three individuals in the devel-
oped world and is more common in patients
with severe obesity and diabetes.3,7,8 Mortality
and disease evolution to fi
osis or ci
hosis is
increased in older patients with NAFLD.3
Cardiovascular disease-related events are
the most common causes of mortality in
patients with NAFLD.3 NASH, which is a pro-
gression from simple fatty liver disease to
infl ammation and injury, is the third most common
cause of liver disease requiring a liver transplant in the
United States.3,4,7 According to Charlton and colleagues, by
2020, NASH will be the leading cause of liver transplant in
the United States.9 Patients with NASH can progress to
ci
hosis and/or HCC.
■ Pathophysiology of NAFLD
The pathophysiology of NAFLD is complex and not com-
pletely understood. Day and James sought to describe the
process of fatty liver disease progression as the “two hits
By Amanda Chaney, MSN, ARNP, FNP-BC
2.0
CONTACT HOURS
1.0
CONTACT HOURS
Keywords: lifestyle modifi cations, liver disease, nonalcoholic fatty liver disease
Abstract: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide
health crisis. It is important for NPs to understand the spectrum of
NAFLD. Although lifestyle modifi cations are the fi rst-line treatment,
the NP should be aware of cu
ent and future medication
management to help the patient live a healthy life.
N
fatty liver disease
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
38 The Nurse Practitioner • Vol. 40, No. 11 www.tnpj.com
Treating the patient with nonalcoholic fatty liver disease
theory.12” In the fi rst hit, steatosis, or fatty infi ltration in the
liver, occurs from issues with insulin resistance and fatty
acid metabolism.2,10-12 Increased free fatty acid to the liver
causes hepatic steatosis. Insulin resistance increases lipolysis
from adipose tissue. This process leads to release of proin-
fl ammatory cytokines (tumor necrosis factor [TNF]-alpha
and interleukin-6), oxidative stress, and infl ammation.13
These, along with molecular endotoxins and genetic factors,
are thought to contribute to the second hit.2,4,14,15 The second
hit results in oxidative stress and steatohepatitis.12
Dietary choices can also play a part. With high amounts
of cholesterol to the liver (either from diet or genetics),
fatty acids are converted to nontriglyceride metabolites.
These particles contribute to hepatocyte injury. High con-
sumption of sugar—particularly fructose—reduces intracel-
lular adenosine triphosphate and is converted to fat, which
is deposited in the liver.5 Collagen is deposited in the liver
and causes fi
osis as infl ammation and liver injury occur.4
As this process continues, fi
osis can turn into ci
hosis
and/or HCC. As the hepatocytes become fatty, patients are
at higher risk for developing diabetes mellitus, cardiovas-
cular disease, and complications related to these diseases.7
■ Diagnosing NAFLD
It may be diffi cult to know when to suspect NAFLD, since
most patients are asymptomatic.4,5,7 Some symptoms that
present are vague, including abdominal discomfort, fatigue,
and nausea.2 Higher-risk patients include patients who have
type 2 diabetes mellitus and who are obese. These patients
are not only at higher risk for liver disease progression but
also cardiovascular disease and death.7 There is cu
ently
no diagnostic screening tool or recommendations for
screening for NAFLD in primary care, even if a patient has
several risk factors to suggest this disease.3 In most cases,
NAFLD is found incidentally when a patient has elevated
liver enzymes or when it is seen on radiologic imaging stud-
ies as hepatic steatosis.2,4
History. A complete history should be obtained in the
patient who has liver disease when NAFLD is suspected.
Occasional symptoms that may occur include right upper
quadrant abdominal pain, pruritus, and jaundice. Gener-
ally, the patient is without symptoms. Other etiologies of
liver disease should be excluded. Cu
ent lifestyle and dietary
habits, including alcohol consumption history, should be
noted. Social history should include cu
ent or prior intra-
vascular or other illicit drug use, blood transfusions, and
sexual activity.4
Physical exam. Physical exam should include vital signs,
height, weight, body mass index (BMI), BP, and waist cir-
cumference. Hepatosplenomegaly may be present if the
patient has evidence of portal hypertension.2,4 Dorsocervi-
cal lipohypertrophy, an increased amount of fat distribution
along the cervical spine, may be present and has been noted
in patients with NASH.16
Lab fi ndings. Labs to exclude other causes of liver disease
include: total protein, alanine aminotransferase (ALT), as-
partate aminotransferase (AST), alkaline phosphatase, albu-
min, total bilirubin, hepatitis B surface antigen, hepatitis C
antibody, fe
itin, iron, fasting blood glucose, hemoglobin
A1C, lipid panel, and low-density lipoprotein cholesterol,
prothrombin time, and insulin levels.4
Patients with NAFLD commonly have elevated fe
itin
levels, and 20% have elevated uric acid levels.2,3 Most patients
with NAFLD will have a mild elevation of AST and ALT,
although some will be normal.2 There are no imaging or
iomarker tests that can differentiate between hepatic ste-
atosis and NASH.8 Cytokeratin-18 fragment levels are the
most researched tool to predict NASH, which is an indicator
of hepatocyte apoptosis.7
Radiologic fi ndings. Imaging studies to evaluate for
NAFLD could include ultrasound, computed tomography
(CT), or magnetic resonance imaging (MRI). Ultrasound
cannot identify infl ammation or fi
osis, but it is the fi rst
imaging study done to evaluate for hepatic steatosis, for
which it has a sensitivity of 60% to 94% and specifi city of
66% to 97%.4,7 It is inexpensive and extensively available.
CT scan can be done to assess the structure of the liver.4 It
is an option for determining hepatic steatosis; however, there
is signifi cant radiation associated with this imaging study.7
MRI is accurate for quantifying the extent of hepatic steato-
sis, but it is expensive.4 Magnetic resonance spectroscopy is
accurate in identifying steatosis and has the potential to
ecome an ideal test for grading and determining the
Defi nition of signifi cant alcohol consumption3
Men
Greater than 21 drinks per week over a 2-year period
Women
Greater than 14 drinks per week over a 2-year period
1 drink = ~10 g alcohol
Risk factors for development of NAFLD3,4,8
• Age, older than 45
• Diabetes mellitus
• Hispanic ethnicity
• Portal hypertension
• Insulin resistance
• Metabolic syndrome
• Obesity
• Family history signifi cant for metabolic syndrome,
cardiovascular disease, chronic liver disease
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Treating the patient with nonalcoholic fatty liver disease
www.tnpj.com The Nurse Practitioner • November XXXXXXXXXX
presence of steatosis; however, it is
costly and with limited availability.7
Noninvasive measures. Risk
scores, such as the NAFLD fi
osis
score and the NASH test, have been
used to try to determine patients
who have NASH but can be inaccu-
ate (see Noninvasive fi
osis scoring
tools).5,17-19 Transient elastography is
a newer imaging study on the hori-
zon. Described as a pulse-echo ultra-
sound, it has shown usefulness in
determining the presence of fi
osis.
This may be helpful in determining
if liver biopsy is necessary.7
Liver biopsy. Liver biopsy is the
gold standard for determining if
NAFLD is present and for staging
severity of disease.7 Complications, including bleeding and
infection, occur in 1% to 3% of patients; death occurs in
0.01% of patients.7 Misdiagnosis can occur in many cases.
Staging and diagnosis are subjective and can vary by the
pathologist.7 Additionally, there is a higher risk of complica-
tion and diffi culty obtaining an adequate sample in patients
who are obese.7
A liver biopsy should be considered in patients with
highly elevated liver function tests (LFTs) or patients with
elevated LFTs and a normal BMI.4 The pathology report may
include fi ndings indicative of NAFLD such as: Mallory hya-
line, hepatocyte ballooning, and lymphocytic and neutro-
philic infl ammatory infi ltrate in perivenular areas. Other
fi ndings may state hepatocyte necrosis, apoptosis, and degree
of fi
osis—graded and staged.4,8
■ NAFLD treatment options
Patients with NAFLD without liver injury have an excellent
prognosis, and their management is primarily aimed at
prevention and reversal of hepatic injury and fi
osis.3-5 The
aim is to prevent progression to ci
hosis and