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Hepatomegaly: Differential diagnosis and evaluation

Authors: Michael P Curry, MD, Alan Bonder, MD
Section Editor: Sanjiv Chopra, MD, MACP
Deputy Editor: Kristen M Robson, MD, MBA, FACG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Nov 2019. | This topic last updated: Apr 30, 2018.

INTRODUCTION

Hepatomegaly is enlargement of the liver beyond its normal size and occurs mainly as a
consequence of pathologic conditions (table 1).

This topic will review how to determine the size of the liver, the differential diagnosis of
hepatomegaly, and the approach to the evaluation of a patient with hepatomegaly. More detailed
discussions of many of the conditions that cause hepatomegaly are presented elsewhere. (See
"Alcoholic hepatitis: Clinical manifestations and diagnosis" and "Overview of autoimmune hepatitis"
and "Clinical manifestations and natural history of chronic hepatitis C virus infection" and "Hepatitis B
virus: Clinical manifestations and natural history" and "Epidemiology, clinical features, and diagnosis
of nonalcoholic fatty liver disease in adults" and "Overview of inherited disorders of glucose and
glycogen metabolism" and "Wilson disease: Clinical manifestations, diagnosis, and natural history"
and "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Congestive
hepatopathy".)

LIVER ANATOMY

Normal size — The liver is wedge-shaped and is present in the right upper quadrant of the abdomen
(figure 1). The liver typically extends from the fifth intercostal space to the right costal margin in the
midclavicular line. The size of the liver increases with age, from an average span of 5 cm at the age of
five years, to 15 cm in adulthood [1]. The size of the normal liver also varies with sex and body size [2-
4]. The normal liver weighs 1.4 to 1.5 kg in men and 1.2 to 1.4 kg in women [1]. Relative to body size,
the liver is larger in the fetus (1/18 of total body weight) than in the adult (1/36 of total body weight)
[1].

By ultrasound, a normal liver is less than 16 cm in the midclavicular line [4]. In a study of 2080
patients who underwent transabdominal ultrasonography, the average liver span in the midclavicular
line was 14.0 +/- 1.7 cm, with 74 percent having a liver span of 15 cm or less [4]. Fourteen percent
had a liver span of 15 to 16 cm, and 12 percent had a liver span of >16 cm. On multivariable analysis,
liver span correlated directly with height and body mass index and was greater in men.

Normal anatomy — Classically, the liver is divided into right and left lobes (figure 2). In the normal
liver, the right lobe is larger than the left lobe and occupies the right hypochondrium. The smaller left
lobe is flatter and is situated in the epigastrium and left hypochondrium.

The liver can be subdivided into eight segments based on vascular supply, each containing branches
of the portal vein, hepatic artery, hepatic vein, and bile ducts (figure 3). There are no surface fissures
or anatomic landmarks demarcating the individual segments.

Anatomic variations — Anatomic variations of the liver may be confused with hepatomegaly. Riedel's
lobe is a downward, tongue-like projection of the right lobe of the liver that on imaging may give the
false impression of hepatomegaly [5,6]. The exact etiology is unknown. It has been described as an
accessory lobe with an incidence that varies from 3 to 31 percent [6]. Since Riedel's lobe is a benign
condition, no treatment is necessary.

The left lobe of the liver can also be elongated and is described as a "beaver-tailed liver." In this case,
a large left hepatic lobe may be confused with hepatomegaly or the left lobe hypertrophy that can be
seen in patients with cirrhosis.

Another anatomic variation that may be confused with hepatomegaly is projection of a papillary
process from the caudate lobe (segment I) (figure 3). The caudate lobe papillary process may extend
posteriorly, lying between the inferior vena cava (IVC) and aorta. Occasionally, the papillary process
will wrap around the IVC such that its tip lies posterior to the IVC. This position of the papillary
process creates the potential for its misdiagnosis as hepatomegaly on imaging studies.

ESTIMATING LIVER SIZE

Hepatomegaly may be suspected based on physical examination findings or hepatic imaging.

Although percussion and palpation of the liver are commonly used clinical methods for determining
liver size, radiologic methods are used frequently to assess the liver size and texture, and to look for
signs of chronic liver disease, focal liver masses, or evidence of portal hypertension. Diagnostic
imaging techniques are superior to clinical examination in determining the size of the liver [7,8].
Physical examination — The liver is the largest organ in the body, but accurate clinical assessment of
the precise size of the liver is difficult. The size of the liver will vary depending on the examining
technique. Percussion in the midclavicular line is the favored physical examination technique to
determine the span of the liver. However, physical examination findings are not reliable for detecting
hepatomegaly [9-12].

The upper border of the liver is assessed using a heavy percussion technique. Light percussion is
used to locate the lower edge of the liver. Light percussion is required because heavy percussion may
underestimate the lower extent of the liver border [7,13]. In a normal liver, the upper border will be in
the fifth intercostal space or behind the sixth rib, and the lower extent will be at or slightly below the
right costal margin. Percussion alone may underestimate liver size because the lower border of the
liver may seem resonant to percussion, particularly if percussion is performed too heavily. If the
distance from the upper border of the liver to the percussed or palpated liver edge is less than 13 cm,
then true hepatomegaly is unlikely [13].

Palpation of the liver is also used to determine the shape and consistency of the liver. The examining
hand is placed below the level of the dull percussion note in the mid-clavicular line, parallel to the
rectus muscle. The liver is palpated during deep inspiration as it moves inferiorly to meet the finger
tips. The liver edge may be tender in patients with acute hepatitis or heart failure, or it may be hard
and irregular in patients with cirrhosis or metastatic disease. Unfortunately, the assessment of liver
consistency, nodularity, and tenderness is unreliable, even among expert examiners [10].

Another technique commonly used for assessing liver size is the "scratch test." The diaphragm of the
stethoscope is placed at the lower costal margin while the abdominal wall is scratched lightly. When
scratching occurs over the lower part of the liver, the scratching sound should seem louder on
auscultation. Unfortunately, correlation between the scratch test and ultrasound assessment of liver
size is moderate at best [11,12].

In a large Italian study of 100 normal controls and 100 patients with liver cirrhosis, there was poor
correlation between clinical exam and ultrasound assessment of liver span in healthy controls, with a
chance-corrected agreement index of 0.13. Correlation was better in patients with cirrhosis (kappa =
0.93). The lower edge of the liver was palpable in 47 percent of controls and in 78 percent of patients
with cirrhosis. Liver span estimated by clinical exam was 11.8 cm in patients with cirrhosis and 9.5
cm in controls, whereas ultrasound-measured liver span was 10.9 and 12.4 cm, respectively [9]. A
similar study from a rural Indian hospital showed that there was poor interobserver agreement among
three clinicians who detected hepatomegaly by palpation of lower liver edge and by percussion for
liver span. In addition, clinical estimates of liver span correlated poorly with findings on
ultrasonography [10].
Ultrasonography — Ultrasonography is an accurate method for determining liver size. In an autopsy
study of 36 patients who had undergone ultrasonography within one month of death, ultrasound was
87 percent accurate in determining whether hepatomegaly was present [14].

Cross-sectional imaging — Both computed tomography (CT) scanning and magnetic resonance

imaging (MRI) can be used to determine liver size and volume [15]. Volumetric assessment
traditionally has required manual contour tracing, segmentation of the organ in question, and
application of mathematical algorithms to determine the volume. However, automated techniques
have been developed that reduce the need for manual input, and thus the time needed to calculate
volume [16,17]. Automated techniques appear to correlate well with manual contour tracing for
volume determination (correlation coefficient of 0.98 in one MRI study) [16].

CT is routinely used to measure total liver volume and segmental liver volume as part of the
preoperative assessment for partial liver resections [15]. Early studies using cadaveric livers showed
that there was minimal discrepancy (<5 percent) between liver volume assessed by CT scan and
water displacement [18].

CT has also been used to determine liver volume in patients with cirrhosis and chronic liver disease.
One study using CT found that liver volume decreases with increasing Child-Pugh score in patients
with cirrhosis [19]. Liver volume appears to vary depending on the etiology of liver disease. Patients
with cholestatic liver disease have larger livers than those with alcoholic/viral hepatitis, while those
with cryptogenic cirrhosis have the smallest livers [20].

DIFFERENTIAL DIAGNOSIS

Hepatomegaly occurs mainly as a consequence of pathologic conditions, though there are settings in
which a normal liver may be palpable on examination. (See 'Anatomic variations' above.)

A normal liver may be palpable below the right costal margin:

● In thin people
● During deep inspiration
● In the setting of a right pleural effusion
● When emphysema results in hyperinflation of the chest with diaphragmatic descent and
downward displacement of the liver

Pathologic conditions that cause hepatomegaly include (table 1) [21]:

● Hepatitis
 • Infection (viral, bacterial, fungal, parasitic)
• Ischemia
• Drug or toxin exposure
• Alcoholic steatohepatitis
• Nonalcoholic steatohepatitis
• Autoimmune hepatitis
• Wilson disease

● Storage disorders (triglycerides, glycogen, glycolipids, protein, iron)

• Alcoholic and nonalcoholic fatty liver disease

• Acute fatty liver disease of pregnancy
• Glycogen storage diseases
• Gaucher disease
• Alpha-1 antitrypsin deficiency
• Hemochromatosis

● Infiltration of the liver

• Granulomatous disease
• Amyloidosis
• Malignancy
• Benign liver tumors

● Impaired hepatic venous outflow

• Right heart failure

• Budd-Chiari syndrome
• Sinusoidal obstruction syndrome (hepatic veno-occlusive disease)
• Peliosis hepatis

● Biliary tract disorders

• Primary biliary cirrhosis

• Primary sclerosing cholangitis
• Biliary atresia

● Miscellaneous

• Caroli disease
• Polycystic liver disease
Typically, other symptoms or clinical findings are present in patients with pathologic conditions that
result in hepatomegaly. Rare instances of true hepatomegaly can occur in normal circumstances and
are considered normal variants, such as Reidel's lobe. (See 'Anatomic variations' above.)

Hepatitis — Hepatic inflammation is a nonspecific reaction to liver damage and may result in

hepatomegaly. Some causes of hepatic inflammation include infection (viral, bacterial, fungal, or
parasitic), drug toxicity, ischemia, alcoholic steatohepatitis, nonalcoholic fatty liver disease, and
autoimmune hepatitis. As an example, in a study of patients with acute hepatitis A or E infection, 23
to 33 percent of patients had hepatomegaly at the time of presentation [22]. (See "Approach to the
patient with abnormal liver biochemical and function tests", section on 'Elevated serum
aminotransferases'.)

Chronic hepatitis and early compensated cirrhosis can remain asymptomatic for some time, and
hepatomegaly may be discovered on routine examination. In patients with cirrhosis, there may be
shrinkage of the enlarged liver with compensatory hypertrophy of the left lobe of the liver, which can
be easily missed if palpation is only performed in the right upper quadrant. (See 'Physical
examination' above.)

Storage disorders — Disorders leading to the abnormal metabolism and storage of triglycerides,

glycogen, glycolipids, protein, or iron may cause hepatomegaly. Common disorders in this category
include alcoholic and nonalcoholic fatty liver disease.

Disorders of lipid metabolism — Disorders of lipid metabolism can result in accumulation of

triglycerides within the liver. Disorders of lipid metabolism may be seen in alcoholic liver disease,
nonalcoholic fatty liver disease, insulin resistance, diabetes mellitus, and acute fatty liver of
pregnancy. The accumulation of triglycerides results from excess delivery to and decreased export of
free fatty acids from the liver. In addition, there is impaired beta oxidation of fatty acids within the
liver. The accumulation of triglycerides results in fatty liver disease and hepatomegaly. (See
"Pathogenesis of alcoholic liver disease" and "Pathogenesis of nonalcoholic fatty liver disease" and
"Acute fatty liver of pregnancy".)

Lysosomal acid lipase deficiency (also referred to as cholesteryl ester storage disease) is another
disorder that may be associated with fatty liver and hepatomegaly. Lysosomal acid lipase deficiency
disease is a mild phenotype of lysosomal acid lipase deficiency (MIM #278000) that presents with
hepatomegaly and fatty liver in childhood or adulthood, depending on the lysosomal acid lipase
activity. This disorder is characterized by hepatic accumulation of cholesteryl esters and triglycerides,
elevated serum aminotransferases, and dyslipidemia with accelerated atherosclerotic disease [23]. A
fulminant infantile form is known as Wolman disease. (See "Causes and clinical manifestations of
primary adrenal insufficiency in children", section on 'Defects in cholesterol biochemistry' and
"Nonalcoholic fatty liver disease in children and adolescents", section on 'Tests to exclude other liver
diseases'.)

Disorders of glycogen metabolism — There are numerous inborn errors of metabolism that result
in glycogen storage disorders, including glucose-6-phosphatase deficiency (GSD I), glycogen
debrancher deficiency (GSD III), liver phosphorylase deficiency (GSD IV), and liver phosphorylase
kinase deficiency (GSD IXa1). These disorders are typically diagnosed in neonates, infants, and young
children. In addition to hepatomegaly, patients with glycogen storage disorders may present with
fasting hypoglycemia and ketosis. (See "Overview of inherited disorders of glucose and glycogen
metabolism".)

Glycogen accumulation within hepatocytes may also be seen in patients with poorly controlled
diabetes mellitus [24,25]. Glycogenic hepatopathy is distinct from steatohepatitis. Serum
aminotransferases can range from 50 to 1600 international unit/L, and steatosis is usually absent on
liver biopsy [24]. In one series, hepatomegaly was present in 78 percent of patients with glycogenic
hepatopathy [26]. Improved glycemic control can result in improvement of symptoms and
aminotransferases, and hepatomegaly can be reversed.

Gaucher disease — Gaucher disease is a lysosomal storage disorder that affects the recycling of
cellular glycolipids, resulting in their accumulation in the lysosomes of macrophages in the liver,
spleen, and bone marrow. Hepatomegaly is universal, with a typical increase in liver volume of two- to
three-times normal [27]. Increases in spleen volume are even larger. Hepatosplenomegaly may be
asymptomatic or may be associated with early satiety, abdominal pain, anemia, and
thrombocytopenia. (See "Gaucher disease: Pathogenesis, clinical manifestations, and diagnosis".)

Alpha-1 antitrypsin deficiency — Liver disease in alpha-1 antitrypsin deficiency is caused by

pathologic polymerization of the variant alpha-1 antitrypsin, resulting in intra-hepatocyte
accumulation of alpha-1 antitrypsin molecules. Patients with hepatic forms of alpha-1 antitrypsin
deficiency may develop hepatomegaly with elevated aminotransferase levels, ascites, and cirrhosis.
Patients with alpha-1 antitrypsin deficiency typically have emphysema. (See "Extrapulmonary
manifestations of alpha-1 antitrypsin deficiency", section on 'Hepatic disease'.)

Hemochromatosis — Hereditary hemochromatosis is an autosomal recessive disorder in which

mutations in the HFE gene cause increased intestinal iron absorption. Progressive iron deposition in
the liver is associated with hepatomegaly, elevated liver enzymes, and the eventual development of
fibrosis and cirrhosis. Patients with hemochromatosis may also have extreme fatigue, skin
hyperpigmentation, diabetes mellitus, arthralgias, impotence, and electrocardiographic abnormalities.
(See "Clinical manifestations and diagnosis of hereditary hemochromatosis", section on 'Hepatic iron
overload'.)
Infiltration of the liver — Hepatomegaly can result from infiltration of the liver with granulomas,
amyloid, malignant tumors, or benign tumors.

Granulomatous disease — Granulomas can be present in the liver in a wide variety of conditions,

such as infection, malignancy, autoimmune conditions, and drug-induced liver injury. In up to one-third
of patients, the cause of hepatic granulomas is unclear [28]. Presenting features may include fever,
night sweats, anorexia, weight loss, malaise, and hepatomegaly. The most common causes of
hepatic granulomas in the United States are sarcoidosis, mycobacterial infection, primary biliary
cirrhosis, and drug reactions [29]. (See "Hepatic granulomas", section on 'Differential diagnosis'.)

Hepatic amyloidosis — Hepatic amyloidosis occurs in the setting of primary (AL) or secondary

(AA) amyloidosis. In a series of 98 patients with hepatic amyloid, hepatomegaly was seen in 81
percent [30]. Other signs and symptoms of systemic illness included weight loss, abdominal pain,
anorexia, ascites, edema, and splenomegaly. Hepatic amyloidosis should be considered in patients
with hepatomegaly and involuntary weight loss, an unexplained elevated alkaline phosphatase, or
proteinuria. (See "Gastrointestinal amyloidosis: Clinical manifestations, diagnosis, and management",
section on 'Hepatic amyloidosis'.)

Hepatosplenic T cell lymphoma — Hepatosplenic T cell lymphoma (HSTCL) is another cause of

hepatomegaly. It is rare, accounting for <1 percent of non-Hodgkin lymphomas (NHL) [31]. In one
series, marked hepatomegaly was present in 84 percent and splenomegaly in 100 percent of patients
with HSTCL [32].

The predominant laboratory findings in patients with HSTCL include pancytopenia, marked
thrombocytopenia, and mildly abnormal aminotransferases and alkaline phosphatase, not dissimilar
to chronic liver diseases. Patients usually have other symptoms, such as fever, night sweats, and
weight loss. The liver is diffusely enlarged as liver sinusoids are markedly expanded by the
lymphoma, and liver biopsy or splenectomy is required to make the diagnosis. (See "Clinical
manifestations, pathologic features, and diagnosis of hepatosplenic T cell lymphoma".)

Malignant tumors — Hepatomegaly may be seen in the setting of hepatic infiltration by solid

tumors. Primary liver tumors that may cause hepatomegaly include hepatocellular carcinoma,
cholangiocarcinoma, and hemangioendothelioma. Patients with a large burden of hepatic
metastases may also have hepatomegaly. (See "Clinical features and diagnosis of hepatocellular
carcinoma", section on 'Clinical features'.)

Patients who develop hepatocellular carcinoma usually have no symptoms other than those related
to their chronic liver disease. Some patients may have mild to moderate upper abdominal pain, weight
loss, or early satiety. Patients with cholangiocarcinoma may have jaundice, pruritus, abdominal pain,
weight loss, or fever.
 Benign tumors — Benign liver tumors that may cause hepatomegaly include hemangiomas,
adenomas, and focal nodular hyperplasia. These tumors typically will appear as discrete lesions on
hepatic imaging. (See "Solid liver lesions: Differential diagnosis and evaluation".)

Impaired venous outflow — Hepatic congestion may develop if venous outflow from the liver is
impeded. This may be seen with Budd-Chiari syndrome, right heart failure, sinusoidal obstruction
syndrome (hepatic veno-occlusive disease), and peliosis hepatis. All of these disorders lead to
passive congestion of the liver, resulting in hepatomegaly with a firm, smooth, and tender liver edge.

Budd-Chiari syndrome — Budd-Chiari syndrome can be defined as any pathophysiologic process

that results in an interruption or diminution of the normal flow of blood out of the liver. However, as
commonly used, Budd-Chiari syndrome implies thrombosis of the hepatic veins and/or the
intrahepatic or suprahepatic inferior vena cava. An alternative nomenclature that recognizes an
obliterative process involving principally the inferior vena cava ("obliterative hepatocavopathy") has
also been proposed. The term Budd-Chiari syndrome is usually distinguished from two other
conditions that interfere with hepatic venous flow: sinusoidal obstruction syndrome and right heart
failure. (See "Etiology of the Budd-Chiari syndrome", section on 'Etiology'.)

Budd-Chiari syndrome is more common in women and usually presents in the third or fourth decade
of life. Signs and symptoms may include right upper quadrant pain and jaundice. However, patients
with chronic disease may be asymptomatic. With complete obstruction of the hepatic veins, caudate
lobe compensatory hypertrophy may develop because venous drainage of the caudate lobe is
frequently spared. The hypertrophied caudate lobe can eventually compress the intrahepatic portion
of the inferior vena cava, leading to further outflow obstruction, accompanied by the development of
ascites and lower extremity edema.

Right heart failure — Patients with passive congestion of the liver from right heart failure may have
right upper quadrant pain, jaundice, and anorexia. They may also have symptoms such as dyspnea on
exertion, fatigue, lethargy, exertional syncope, and exertional angina. (See "Evaluation of the patient
with suspected heart failure", section on 'Clinical presentation'.)

In cases associated with severe tricuspid regurgitation, the liver is often pulsatile on palpation [33].
However, with progressive disease leading to cardiac cirrhosis, the pulsatility related to tricuspid
regurgitation will disappear. These patients frequently have mild elevations of the serum bilirubin and
serum transaminases. (See "Congestive hepatopathy".)

Sinusoidal obstruction syndrome — Sinusoidal obstruction syndrome is due to non-thrombotic

fibrous obliteration of the hepatic venules. Sinusoidal obstruction syndrome typically occurs in the
context of hematopoietic cell transplantation. However, it may also be induced by the ingestion of
pyrrolizidine alkaloids, usually from herbal sources (such as bush tea and other herbal teas), by high-
dose radiation therapy to the liver (usually exceeding 30 Gy) without cytoreductive chemotherapy, by
radioembolization of liver tumors, and by liver transplantation. As sinusoidal pressure increases,
sinusoidal dilatation, central congestion, and hepatomegaly develop. Long-standing congestion can
cause centrilobular fibrosis, leading to cirrhosis. (See "Diagnosis of hepatic sinusoidal obstruction
syndrome (veno-occlusive disease) following hematopoietic cell transplantation".)

Findings in patients with sinusoidal obstruction syndrome include sudden weight gain, liver
tenderness, peripheral edema, elevated serum aminotransferases, hyperbilirubinemia, confusion,
bleeding, renal insufficiency, and cardiopulmonary failure. (See "Diagnosis of hepatic sinusoidal
obstruction syndrome (veno-occlusive disease) following hematopoietic cell transplantation", section
on 'Clinical features'.)

Peliosis hepatis — Peliosis hepatis is an uncommon condition characterized by large blood-filled

cavities not lined by sinusoidal cells. It may be associated with anabolic steroid use and
immunocompromised states [34]. It can present with fever, hepatomegaly, portal hypertension, and
ascites. (See "Peliosis hepatis".)

Biliary tract disorders — Hepatomegaly is present in the majority (70 percent) of patients with
advanced primary biliary cirrhosis (PBC) [35]. It is also present in 55 percent of patients with primary
sclerosing cholangitis (PSC) and is the most frequent clinical finding noted at the time of diagnosis
[36,37]. (See "Primary sclerosing cholangitis in adults: Clinical manifestations and diagnosis", section
on 'Clinical manifestations' and "Clinical manifestations, diagnosis, and prognosis of primary biliary
cholangitis (primary biliary cirrhosis)", section on 'Physical examination'.)

One study found that at the time of liver transplantation, patients with cirrhosis due to cholestatic
liver disease had larger livers than patients with hepatocellular disease, regardless of the severity of
the cirrhosis [20]. It is not clear why the livers from patients with cholestatic liver disease are larger
than those from patients with viral or alcohol etiology.

Findings in patients with PBC may include fatigue, pruritus, arthritis, and skin hyperpigmentation,
though many patients are asymptomatic. Patients with PSC may report fatigue and pruritus, but they
too may be asymptomatic.

Miscellaneous — Liver cysts may lead to hepatomegaly. Cystic liver lesions may be seen in patients
with Caroli disease or polycystic liver disease. (See "Caroli disease" and "Diagnosis and management
of cystic lesions of the liver", section on 'Polycystic liver disease'.)

Caroli disease is a congenital disorder characterized by multifocal, segmental dilatation of large

intrahepatic bile ducts. The condition is usually associated with renal cystic disease of varying
severity. Patients with Caroli disease may develop abdominal pain, pruritus, bacterial cholangitis,
ascites, and variceal bleeding.

Polycystic liver disease predominantly occurs in patients with autosomal dominant polycystic kidney
disease (ADPKD), with an increasing burden of liver cysts occurring with age and in patients with
more advanced renal disease. Women tend to develop cysts earlier in life, and massive cysts are
more commonly seen in women [38]. Patients with undiagnosed polycystic kidney disease may
sometimes be thought to have hepatosplenomegaly on physical examination due to the significant
size of the kidney cysts. (See "Diagnosis and management of cystic lesions of the liver", section on
'Polycystic liver disease'.)

Less commonly seen is an autosomal dominant polycystic liver disease not associated with renal
cystic disease (ADPLD). Most patients are asymptomatic, but with progressive enlargement and an
increasing number of cysts, patients can present with progressive pain, abdominal distension,
nausea, and early satiety. Partial hepatic resections, fenestration of liver cysts, liver transplantation, or
combined liver and kidney transplantation have been offered to patients with debilitating symptoms
[39,40].

CLINICAL MANIFESTATIONS

Patients with hepatomegaly are often asymptomatic from the hepatomegaly itself. However, patients
may report right upper quadrant pain or symptoms related to the underlying disorder causing the
hepatomegaly. The signs, symptoms, and laboratory findings will vary based on the underlying cause
of the hepatomegaly. (See 'Differential diagnosis' above.)

DIAGNOSTIC APPROACH

The diagnostic approach to the patient with hepatomegaly is similar to the evaluation of patients with
abnormal liver biochemical and function tests (LFTs). The initial evaluation includes obtaining a
history to identify potential risk factors for liver disease and performing a physical examination to
look for clues to the etiology and for signs of chronic liver disease. Laboratory testing should be
performed to look for abnormalities, such as hematologic and LFT abnormalities. Subsequent testing
is determined based on the information gathered from the history, physical examination, and blood
tests, and may include additional laboratory tests, paracentesis, imaging studies, or endoscopic
evaluation (eg, endoscopic retrograde cholangiopancreatography). (See "Approach to the patient with
abnormal liver biochemical and function tests" and "Evaluation of adults with ascites".)
An evaluation for systemic diseases should be pursued in patients with a history, signs, or symptoms
of a systemic disease that may be associated with hepatomegaly (eg, sarcoidosis, tuberculosis,
amyloidosis, malignancy, glycogen storage diseases). Typically, such patients will have symptoms
associated with the underlying disease. (See 'Differential diagnosis' above and "Gastrointestinal,
hepatic, pancreatic, and peritoneal sarcoidosis" and "Gastrointestinal amyloidosis: Clinical
manifestations, diagnosis, and management" and "Overview of inherited disorders of glucose and
glycogen metabolism" and "Overview of inherited disorders of glucose and glycogen metabolism",
section on 'Liver disorders' and "Clinical manifestations, diagnosis, and treatment of miliary
tuberculosis", section on 'Clinical manifestations'.)

SUMMARY

● The liver typically extends from the fifth intercostal space to the right costal margin in the
midclavicular line. The size of the normal liver varies with age, sex, and body size. By ultrasound,
a normal liver is less than 16 cm in the midclavicular line. (See 'Liver anatomy' above.)

● Hepatomegaly may be suspected based on physical examination findings or hepatic imaging.

Although percussion and palpation of the liver are commonly used clinical methods for
determining liver size, radiologic methods are superior to clinical examination in determining the
size of the liver. (See 'Estimating liver size' above.)

● Hepatomegaly occurs mainly as a consequence of pathologic conditions, though there are

settings in which a normal liver may be palpable on examination. Typically, other symptoms or
clinical findings are present in patients with pathologic conditions that result in hepatomegaly.
(See 'Anatomic variations' above.)

● A normal liver may be palpable below the right costal margin:

• In thin people
• During deep inspiration
• In the setting of a right pleural effusion
• When emphysema results in hyperinflation of the chest with diaphragmatic descent and
downward displacement of the liver

● Pathologic conditions that cause hepatomegaly include (table 1) (see 'Differential diagnosis'
above):

• Hepatitis: Infection (viral, bacterial, fungal, parasitic), ischemia, drugs, toxins, alcoholic
steatohepatitis, nonalcoholic steatohepatitis, autoimmune hepatitis, Wilson disease (see
'Hepatitis' above)
 • Storage disorders: Alcoholic and nonalcoholic fatty liver disease, acute fatty liver disease of
pregnancy, glycogen storage diseases, Gaucher disease, alpha-1 antitrypsin deficiency,
hemochromatosis (see 'Storage disorders' above)

• Infiltration of the liver: Granulomatous disease, amyloidosis, malignancy, benign liver tumors
(see 'Infiltration of the liver' above)

• Impaired hepatic venous outflow: Right heart failure, Budd-Chiari syndrome, sinusoidal
obstruction syndrome, peliosis hepatis (see 'Impaired venous outflow' above)

• Biliary tract disorders: Primary biliary cirrhosis, primary sclerosing cholangitis, biliary atresia
(see 'Biliary tract disorders' above)

• Miscellaneous: Caroli disease, polycystic liver disease (see 'Miscellaneous' above)

● The diagnostic approach to the patient with hepatomegaly is similar to the evaluation of patients
with abnormal liver biochemical and function tests (LFTs). The initial evaluation includes
obtaining a history to identify potential risk factors for liver disease and performing a physical
examination to look for clues to the etiology and for signs of chronic liver disease. Laboratory
testing should be performed to look for abnormalities, such as hematologic and LFT
abnormalities. Subsequent testing is determined based on the information gathered from the
history, physical examination, and blood tests. (See 'Diagnostic approach' above.)

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Topic 89223 Version 11.0

GRAPHICS

Causes of hepatomegaly

Hepatitis
Infections
Acute and chronic viral hepatitis

Bacterial liver abscess

Parasitic infections

Granulomatous hepatitis

Ischemia
Ischemic hepatitis ("shock liver")

Toxins
Alcoholic hepatitis

Steatosis
Alcoholic fatty liver disease

Nonalcoholic steatohepatitis

Medications
Drug induced liver injury (DILI)

Immune mediated hepatitis

Autoimmune hepatitis

Copper deposition
Wilson disease

Storage disorders
Glycogen
Glycogen storage disorders

Diabetes mellitus

Lipid
Gaucher disease

Nonalcoholic steatohepatitis

Protein
Alpha-1 antitrypsin deficiency

Iron
Hemochromatosis

Impaired venous outflow

Cardiac
Right heart failure

Constrictive pericarditis

Hepatic vein or inferior vena cava obstruction

Hepatic vein thrombosis

Inferior vena cava web

Intrahepatic
Sinusoidal obstruction syndrome

Peliosis hepatis

Infiltrative disease affecting the liver

Benign primary liver tumors
Hemangiomas

Adenomas
 Focal nodular hyperplasia

Malignant primary liver tumors

Hepatocellular carcinoma

Cholangiocarcinoma

Fibrolamellar carcinoma

Hemangioendothelioma

Metastatic/disseminated tumors
Myeloma

Lymphoma

Leukemia

Metastatic solid tumors

Biliary obstruction/cholestatic diseases

Primary biliary cirrhosis

Primary sclerosing cholangitis

Biliary atresia

Miscellaneous
Anatomic variations
Riedel's lobe

Cystic liver disease

Polycystic liver disease

Caroli's disease

Graphic 90714 Version 1.0

Adult abdominal anatomy

Graphic 51176 Version 2.0

Surfaces of the liver

Graphic 67698 Version 2.0

Segmental anatomy of liver

Drawing depicting the functional segments of the liver (Couinaud's segments). Segments II to IV make up the left
lobe and segments V to VIII constitute the right lobe.

Graphic 81897 Version 3.0

Contributor Disclosures
Michael P Curry, MD Grant/Research/Clinical Trial Support: Conatus [Liver fibrosis (Investigational product
called IDN6556)]; Mallinckrodt [Hepatorenal syndrome (Investigational product called Emricassan0)]; Gilead
[Hepatitis C]; Prometheus (NAFLD); TRIO Health Analytics (HBV). Consultant/Advisory Boards: Gilead [Hepatitis
C]; Bristol-Myers Squibb [Hepatitis C] [HCC]; AbbVie [Hepatitis C]; Trio Health Analytics [HCV] [HBV]. Alan Bonder,
MD Nothing to disclose Sanjiv Chopra, MD, MACP Nothing to disclose Kristen M Robson, MD, MBA,
FACG Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
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