Radiologic Mimics of Cirrhosis

G a s t r o i n t e s t i n a l I m a g i n g • P i c t o r i a l E s s ay
Jha et al.
Radiologic Mimics of Cirrhosis
Gastrointestinal Imaging
Pictorial Essay
Radiologic Mimics of Cirrhosis
Priyanka Jha1
Liina Poder
Zhen J. Wang
Antonio C. Westphalen
Benjamin M. Yeh
Fergus V. Coakley
Jha P, Poder L, Wang ZJ, Westphalen AC, Yeh BM,
Coakley FV
OBJECTIVE. The objective of this article is to provide a practical review of the conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal
hypertension.
CONCLUSION. Conditions that can mimic cirrhosis on imaging include pseudocirrhosis of treated breast cancer metastases to the liver, fulminant hepatic failure, miliary metastases, sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension,
early primary biliary cirrhosis, chronic Budd-Chiari syndrome, chronic portal vein thrombosis, and nodular regenerative hyperplasia.
C
Keywords: cirrhosis, liver, liver disease, pseudocirrhosis
DOI:10.2214/AJR.09.3409
Received July 30, 2009; accepted after revision
September 15, 2009.
Z. J. Wang was supported by an NIBIB training grant
(1 T32 EB001631).
1
All authors: Department of Radiology, University of
California, San Francisco, 505 Parnassus Ave., Box 0628,
M-372, San Francisco, CA 94143-0628. Address
correspondence to F. V. Coakley (Fergus.Coakley@
radiology.ucsf.edu).
CME
This article is available for CME credit.
See www.arrs.org for more information.
AJR 2010; 194:993–999
0361–803X/10/1944–993
© American Roentgen Ray Society
AJR:194, April 2010
T of patients with established cirrhosis shows diffuse surface nodularity of the liver and also may
show decreased liver volume with
relative hypertrophy of the left and caudate
lobes or signs of portal hypertension. When
seen at imaging, diffuse hepatic surface nodularity or signs of portal hypertension (i.e.,
splenomegaly, ascites, or portosystemic varices) are usually due to cirrhosis, but other
conditions can also cause these findings.
Knowledge of radiologic mimics of cirrhosis
is increasingly important because some have
been described only recently and because an
erroneous diagnosis of cirrhosis in some settings could adversely impact contemporary
treatment options. For example, underlying
cirrhosis lowers the transplantation status of
patients with acute hepatic failure. This article
aims to provide a practical and current review
of the conditions other than cirrhosis that can
result in diffuse hepatic surface nodularity or
signs of portal hypertension.
Noncirrhotic Causes of Diffuse
Hepatic Surface Nodularity
General Comments
Diffuse irregularity of the hepatic contour
may be fine or coarse (Appendix 1). Causes
of coarse lobulation include chronic BuddChiari syndrome, chronic portal vein thrombosis, and pseudomyxoma peritonei [1]. The
hepatic contour changes due to these conditions usually are easily distinguishable from
cirrhosis because of characteristic features.
The nodularity associated with cirrhosis is
typically relatively fine and diffuse rather
than coarse and lobulated [2]. However, noncirrhotic causes of fine, diffuse nodularity are
occasionally encountered and include pseudocirrhosis of treated breast cancer metastases
to the liver, fulminant hepatic failure, miliary
metastases, and sarcoidosis [3–6].
Pseudocirrhosis of Treated Breast Cancer
Metastases to the Liver
A variety of hepatic contour changes can occur in breast cancer patients with metastases to
the liver after chemotherapy including fine, diffuse nodularity that resembles cirrhosis (Fig.
1), which is commonly referred to as “pseudocirrhosis” [3]. Multifocal retraction of the liver capsule and enlargement of the caudate
lobe also can be seen in this setting. The histopathologic or pathophysiologic basis of these
changes is not well understood, and the prefix
“pseudo-” may be a misnomer because these
patients can develop features of portal hypertension such as portosystemic venous collaterals and bland ascites (Figs. 1 and 2). Why this
phenomenon seems almost specific for breast
cancer (Fig. 3) remains unclear, with only sporadic reports of these changes in other primary
malignancies with liver metastases [7].
Fulminant Hepatic Failure
Fulminant hepatic failure constitutes acute
severe impairment of hepatic function in the absence of preexisting liver disease and receives
higher priority for hepatic transplantation than
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Jha et al.
hepatic failure developing in the setting of cirrhosis. The distinction of acute from acute-onchronic hepatic failure may be clinically difficult and hepatic surface nodularity might be
considered indicative of underlying cirrhosis,
adversely impacting transplantation status. Recently, fulminant hepatic failure alone was
shown to result in diffuse surface nodularity because of a combination of alternating foci of
confluent regenerative nodules and necrosis
rather than cirrhosis [8] (Figs. 4 and 5).
Miliary Metastases
Diffuse surface nodularity due to miliary
metastases is rare (Figs. 6 and 7) and is unlikely to mimic cirrhosis. In a large ultrasound study [4] of hepatic metastases (n =
225), surface irregularity was observed in 16
patients (7%); in only two patients, one with
squamous cell carcinoma of the tonsil and one
with ovarian carcinoma, was surface nodularity the only sign of metastatic disease [4].
Sarcoidosis
Sarcoidosis of the liver is common pathologically but is rarely visible at imaging because the noncaseating granulomas are usually microscopic. Occasionally, hepatic
sarcoidosis can be visible as diffuse granular
heterogeneity with or without fine nodularity
of the hepatic surface [5] (Figs. 8 and 9).
Noncirrhotic Causes of Portal
Hypertension
General Comments
Noncirrhotic causes of portal hypertension (Appendix 2) include chronic BuddChiari syndrome, chronic portal vein thrombosis, sarcoidosis, schistosomiasis, nodular
regenerative hyperplasia, congenital hepatic
fibrosis, idiopathic portal hypertension, and
early primary biliary cirrhosis [9].
Nodular Regenerative Hyperplasia
Nodular regenerative hyperplasia is a rare
but increasingly recognized condition characterized by widespread transformation of
normal liver parenchyma into hyperplastic
regenerative nodules that vary in size from
microscopic to large and masslike [10]; the
absence of fibrosis distinguishes nodular regenerative hyperplasia from cirrhosis. From
a radiologic perspective, there appear to be
two forms of the condition: a diffuse form in
which the nodules are small and a widespread
and a focal form in which the nodules are few
in number, are scattered throughout the liver,
and measure up to a few centimeters.
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The pathogenesis of diffuse nodular regenerative hyperplasia is unknown, but there are
well-recognized associations (Appendix 3)
with systemic cardiovascular, myeloproliferative, and autoimmune diseases, particularly
systemic lupus erythematosus; the administration of certain drugs including chemotherapy;
solid organ and bone marrow transplantation;
and HIV infection [10]. Focal nodular regenerative hyperplasia has been primarily reported
in long-standing Budd-Chiari syndrome, although similar masses have also been reported in autoimmune hepatitis [11, 12]. Diffuse
nodular regenerative hyperplasia frequently results in noncirrhotic portal hypertension
[10], and affected patients may present with
variceal bleeding or hypersplenism.
Imaging findings in patients with nodular
hyperplasia can be subtle across all techniques,
although parenchymal findings may be more
obvious on ultrasound than on CT or MRI [13].
At ultrasound, widespread nodularity suggestive of cirrhosis or multiple masses may be
seen (Fig. 10). At CT, the nodules may be hypodense with little enhancement. At MRI, diffuse nodular regenerative hyperplasia is usually of similar signal intensity to the liver on T1,
T2, and gadolinium-enhanced sequences. Surface nodularity and features of portal hypertension may be seen across all techniques (Fig.
11). In focal nodular regenerative hyperplasia,
CT or MRI typically shows multiple hypervascular masses in a patient with long-standing
Budd-Chiari syndrome or autoimmune hepatitis. These masses may suggest metastases or
hepatocellular carcinoma, although stability on
follow-up studies or biopsy should help in making the correct diagnosis.
Early Primary Biliary Cirrhosis
Investigators recently found that portal
hypertension can develop early in primary biliary cirrhosis—even before the onset
of cirrhosis [14]—possibly resulting from
compression of the portal venous branches by granulomatous inflammation causing
presinusoidal fibrosis and portal hypertension [14]. This condition has been described
as the portal hypertensive variant of primary
biliary cirrhosis and appears to carry a higher risk of hepatocellular carcinoma than the
other variants of primary biliary cirrhosis.
Congenital Hepatic Fibrosis
Hepatic involvement in this multisystem autosomal recessive disorder consists
of widespread periportal fibrosis leading to
portal hypertension [15]. Portal vein throm-
bosis is common, and segmental biliary dilatation may also be observed (Fig. 12).
Idiopathic Portal Hypertension
Idiopathic portal hypertension is characterized by long-standing presinusoidal portal hypertension of unknown cause in adults and may
reflect damage to the intrahepatic small portal
veins or portal tracts by an immunologic disturbance, thromboembolism, or an infection.
Imaging findings (Fig. 13) include subcapsular
parenchymal atrophy, portal and parenchymal
fibrosis, and portal venous thrombosis. Interestingly, cirrhosis does not develop even in the
advanced stages of the disease [16].
Conclusion
Diffuse surface nodularity of the liver or
signs of portal hypertension usually reflect underlying cirrhosis, but noncirrhotic causes of
these imaging findings include pseudocirrhosis
of treated breast cancer metastases to the liver,
fulminant hepatic failure, miliary metastases,
sarcoidosis, schistosomiasis, congenital hepatic fibrosis, idiopathic portal hypertension, early
primary biliary cirrhosis, chronic Budd-Chiari
syndrome, chronic portal vein thrombosis, and
nodular regenerative hyperplasia.
Pseudocirrhosis of treated breast cancer metastases can be easily identified by reviewing
the patient’s medical history and prior imaging
examinations. Pseudocirrhosis of fulminant
hepatic failure should be considered in previously healthy patients with acute liver decompensation. Miliary metastases should be considered when fine hepatic surface nodularity is
seen in a patient with a known primary malignancy and no signs of portal hypertension. A
raised serum angiotensin-converting enzyme
level or mediastinal adenopathy suggests sarcoidosis. Congenital hepatic fibrosis should be
considered in children with findings of portal
hypertension, particularly if there are cysts in
the kidneys. A smooth liver of normal size with
features of portal hypertension should raise suspicion for idiopathic portal hypertension, but
biopsy may be required because this diagnosis is one of exclusion. Diffuse nodular regenerative hyperplasia should be considered when
multiple small masses are seen in the liver of a
patient with known risk factors, particularly if
the clinical picture does not favor malignancy
and if the lesions are more prominent at ultrasound than on other techniques. Focal nodular
regenerative hyperplasia should be considered
when multiple hypervascular hepatic masses
are seen in a patient with long-standing BuddChiari syndrome or autoimmune hepatitis.
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Radiologic Mimics of Cirrhosis
Although these distinguishing features may
be helpful, histologic correlation will be required
to diagnose some cases. Careful radiologic analysis and clinical correlation may be required to
prevent an erroneous diagnosis that could potentially adversely impact management.
References
1.Lipson JA, Qayyum A, Avrin DE, Westphalen A,
Yeh BM, Coakley FV. CT and MRI of hepatic
contour abnormalities. AJR 2005; 184:75–81 [Erratum in AJR 2005; 184:1028]
2.Keedy A, Westphalen AC, Qayyum A, et al. Diagnosis of cirrhosis by spiral computed tomography:
a case-control study with feature analysis and assessment of interobserver agreement. J Comput
Assist Tomogr 2008; 32:198–203
3.Qayyum A, Lee GK, Yeh BM, Allen JN, Venook
AP, Coakley FV. Frequency of hepatic contour
abnormalities and signs of portal hypertension at
CT in patients receiving chemotherapy for breast
cancer metastatic to the liver. Clin Imaging 2007;
31:6–10
4.Di Lelio A, Cestari C, Lomazzi A, Beretta L. Cir-
rhosis: diagnosis with sonographic study of the
liver surface. Radiology 1989; 172:389–392
5.Scott GC, Berman JM, Higgins JL Jr. CT patterns
of nodular hepatic and splenic sarcoidosis: a review of the literature. J Comput Assist Tomogr
1997; 21:369–372
6.Brancatelli G, Federle MP, Ambrosini R, et al.
Cirrhosis: CT and MR imaging evaluation. Eur J
Radiol 2007; 61:57–69
7.Kang SP, Taddei T, McLennan B, Lacy J. Pseudocirrhosis in a pancreatic cancer patient with liver metastases: a case report of complete resolution of pseudocirrhosis with an early recognition and management.
World J Gastroenterol 2008; 14:1622–1624
8.Poff JA, Coakley FV, Qayyum A, et al. Frequency
and histopathologic basis of hepatic surface nodularity in patients with fulminant hepatic failure.
Radiology 2008; 249:518–523
9.Kumar V, Abbas AK, Fausto N, Robbins SL,
Cotran RS, eds. Robbins and Cotran pathologic
basis of disease, 7th ed. Philadelphia, PA: Elsevier Saunders, 2005
10.Dachman AH, Ros PR, Goodman ZD, Olmsted
WW, Ishak KG. Nodular regenerative hyperplasia
of the liver: clinical and radiologic observations.
AJR 1987; 148:717–722
11.Qayyum A, Graser A, Westphalen A, et al. CT of
benign hypervascular liver nodules in autoimmune hepatitis. AJR 2004; 183:1573–1576
12.Rha SE, Lee MG, Lee YS, et al. Nodular regenerative hyperplasia of the liver in Budd-Chiari
syndrome: CT and MR features. Abdom Imaging
2000; 25:255–258
13.Casillas C, Marti-Bonmati L, Galant J. Pseudotumoral presentation of nodular regenerative hyperplasia of the liver: imaging in five patients including MR imaging. Eur Radiol 1997; 7:654–658
14.Murata Y, Abe M, Furukawa S, et al. Clinical features of symptomatic primary biliary cirrhosis
initially complicated with esophageal varices. J
Gastroenterol 2006; 41:1220–1226
15.Akhan O, Karaosmanoglu AD, Ergen B. Imaging
findings in congenital hepatic fibrosis. Eur J Radiol 2007; 61:18–24
16.Nakanuma Y, Tsuneyama K, Ohbu M, Katayanagi
K. Pathology and pathogenesis of idiopathic portal hypertension with an emphasis on the liver.
Pathol Res Pract 2001; 197:65–76
APPENDIX 1: Noncirrhotic Causes of Diffuse Hepatic Contour Irregularity
Coarse lobulation
Chronic Budd-Chiari syndrome
Chronic portal vein thrombosis
Pseudomyxoma peritonei
Fine nodularity
Pseudocirrhosis of treated breast cancer metastases to the liver
Fulminant hepatic failure
Miliary metastases
Sarcoidosis
APPENDIX 2: Noncirrhotic Causes of Portal Hypertension
1. Chronic Budd-Chiari syndrome
2. Chronic portal vein thrombosis
3. Sarcoidosis
4. Schistosomiasis
5. Nodular regenerative hyperplasia
6. Congenital hepatic fibrosis
7. Idiopathic portal hypertension
8. Early primary biliary cirrhosis
APPENDIX 3: Associations of Diffuse and Focal Forms of Nodular Regenerative Hyperplasia
Diffuse form
Cardiovascular diseases
Myeloproliferative diseases
Autoimmune diseases, particularly systemic lupus erythematosus
Certain drugs including chemotherapy
Solid organ and bone marrow transplantation
HIV infection
Focal form
Chronic Budd-Chiari syndrome
Autoimmune hepatitis
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A
B
Fig. 1—62-year-old woman with breast cancer treated with chemotherapy.
A, Axial contrast-enhanced CT image obtained after patient had received chemotherapy treatment shows diffuse surface nodularity in liver and recanalized umbilical
vein (arrow); these findings are suggestive of cirrhosis.
B, Axial contrast-enhanced CT image obtained 6 months before A, which was before patient started chemotherapy, shows multiple hepatic metastases. Liver is
otherwise normal. Setting of breast cancer metastases treated with chemotherapy indicates rapid development of diffuse changes seen in A likely represents
pseudocirrhosis of treated breast cancer.
A
B
Fig. 2—59-year-old woman with multiple hypodense biopsy-proven hepatic metastases from invasive ductal carcinoma of breast.
A, Axial contrast-enhanced CT image obtained before patient started chemotherapy.
B, Axial contrast-enhanced CT image obtained 6 months after A—that is, after patient had started chemotherapy—shows diffuse hepatic nodularity, bland ascites
(asterisk), esophageal varices (arrow), and partial regression of hepatic metastases. Findings are of pseudocirrhosis of treated breast cancer metastases; however,
without prior studies and clinical history, these findings could suggest diagnosis of cirrhosis.
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Radiologic Mimics of Cirrhosis
A
B
Fig. 3—68-year-old woman who presented for imaging after receiving two cycles of chemotherapy for hepatic metastases thought to be from primary pancreatic
carcinoma.
A, Axial contrast-enhanced CT image shows liver surface is coarsely lobulated with several irregular hypodense parenchymal lesions. Appearance was considered
suggestive of pseudocirrhosis, casting doubt on diagnosis of pancreatic cancer.
B, Axial contrast-enhanced image obtained at more superior level than A shows small hypervascular lesion (arrow) in right breast. Further workup including resection of
breast mass confirmed diagnosis of metastatic breast cancer.
Fig. 4—61-year-old man with fulminant hepatic
failure and history of chronic hepatitis B infection.
A, Contrast-enhanced CT image shows nodularity
(arrow) of liver surface outlined by ascites; there
findings are suggestive of cirrhosis. Histopathologic
examination of explanted liver 5 days later showed
confluent regenerative nodules surrounded by large
areas of necrosis, but no cirrhosis. Hepatic surface
nodularity is not a reliable sign of underlying cirrhosis
in fulminant hepatic failure and should not be used to
diagnose cirrhosis in this setting.
B, Photomicrograph of explanted hepatic surface
from transplant surgery performed 5 days after
A shows that irregularity of liver surface reflects
combination of confluent regenerative nodules (R)
and alternating bands of necrosis (N). (H and E, ×200)
A
B
Fig. 5—67-year-old woman with fulminant hepatic failure that developed 6 weeks after commencement of
methyldopa therapy for hypertension. Sagittal ultrasound image of right hepatic lobe shows nodularity (arrow)
of liver surface outlined by ascites; there findings are suggestive of cirrhosis. Histopathologic examination
of explanted liver 3 days later showed confluent regenerative nodules surrounded by large areas of subacute
necrosis but no cirrhosis.
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Fig. 6—64-year-old woman with metastatic lobular breast cancer. Axial contrastenhanced CT image shows fine nodularity of hepatic surface. Liver biopsy
revealed metastatic breast cancer without cirrhosis.
Fig. 7—58-year-old woman with bilateral lobular breast cancer. Axial contrastenhanced CT image shows widespread diffuse parenchymal and surface hepatic
nodularity. Biopsy revealed metastatic disease without cirrhosis.
Fig. 8—32-year-old man with sarcoidosis. Axial contrast-enhanced CT image
shows widespread diffuse parenchymal and surface hepatic nodularity (arrow).
Appearance of liver on CT alone could be interpreted as cirrhosis, but note
multiple hypodense nodules in spleen. Retroperitoneal adenopathy (not shown)
was also present. Nodal biopsy confirmed diagnosis of sarcoidosis.
Fig. 9—44-year-old man with sarcoidosis. Axial unenhanced CT image shows
splenomegaly (asterisk) and recanalized umbilical vein (arrow) arising from
somewhat shrunken and irregular liver. Liver biopsy revealed sarcoidosis without
cirrhosis. Sarcoidosis is one cause of noncirrhotic portal hypertension.
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Radiologic Mimics of Cirrhosis
Fig. 10—58-year-old man with history of
renal transplantation for HIV nephropathy
who presented with sepsis 1 day after right
hemicolectomy for colonic volvulus.
A, Sagittal ultrasound image of right
hepatic lobe shows subtle echogenic
nodularity of liver that could be considered
suggestive of cirrhosis. Representative
nodule (arrow) is visible anteriorly.
B, Axial contrast-enhanced CT image
shows subtle parenchymal heterogeneity
consisting of small hypodense nodules.
Representative nodule (arrow) is
visible posteriorly. Subsequent liver
biopsy confirmed diagnosis of nodular
regenerative hyperplasia.
A
Fig. 11—60-year-old man with portal hypertension leading to gastrointestinal
bleeding, ascites, and thrombocytopenia due to biopsy-proven nodular
regenerative hyperplasia in liver transplant; transplantation was performed 18
years earlier for primary sclerosing cholangitis. Axial contrast-enhanced CT
image shows liver surface (arrow) is irregular and shows relative hypertrophy of
left hepatic lobe (asterisk). These findings mimic those of cirrhosis.
B
Fig. 12—11-year-old girl with renal failure due to autosomal recessive polycystic
kidney disease. Coronal T2-weighted MR image shows kidneys (K) are replaced
by innumerable relatively small cysts. Focal segmental biliary dilatation (arrow)
in liver reflects coexistent congenital hepatic fibrosis, which can occur in
association with autosomal recessive polycystic kidney disease and is cause of
noncirrhotic portal hypertension. Note spleen (asterisk) is enlarged.
Fig. 13—68-year-old man with idiopathic portal hypertension. Axial contrast-enhanced
CT image shows splenomegaly (S), gastroesophageal varices (white arrow), and ascites
(black arrow), but liver appears normal in size and contour. Liver biopsy confirmed
absence of cirrhosis; final diagnosis was idiopathic portal hypertension.
F O R YO U R I N F O R M AT I O N
This article is available for CME credit. See www.arrs.org for more information.
AJR:194, April 2010
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