Hepatic Calcifications

Hepatic calcifications are small, punctate areas of abnormal brightness visualized on ultrasound, and have similar echogenicity to that of the surrounding bone.

Highly echogenic liver on ultrasound ICD-10-CM R93.2

The estimated incidence of hepatic calcifications is 1 in 1750.¹

A single hepatic calcification is a relatively common and benign finding identified at the time of the second trimester anatomic survey, and commonly associated with excellent prognosis. Liver calcifications are typically grouped according to their number (single or multiple), location (parenchymal or on the liver surface), and relationship to the liver vessels. Multiple calcifications in the liver or on the surface of the liver increase the likelihood that there is an underlying diagnosis. They may be associated with chromosomal abnormalities, abnormalities of the liver vessels including thrombosis or hemorrhage, fetal infection or meconium peritonitis. 

The typical fetus has a single calcification and no additional abnormalities seen. 
The finding of a hepatic calcification mandates a careful look at the remainder of the fetal anatomic structures to evaluate the fetus for signs of aneuploidy and infection. 
If additional calcifications are detected in the fetal abdominal cavity, brain, or placenta, or if congenital cataracts are seen, the fetus may have an underlying problem.
 

Diagnosis of a hepatic calcification is made with ultrasound. Once a calcification is identified, the liver should be evaluated for additional calcifications and the location of the calcifications (intraparenchymal or on the liver surface) should be evaluated. The placenta, brain, and abdomen should be evaluated to exclude additional calcifications. The lenses in the eye should be evaluated to exclude congenital cataracts. The entire fetus should be evaluated for additional abnormalities which could suggest aneuploidy. Multiple parenchymal calcifications suggest an infectious etiology, while multiple calcifications on the surface of the liver suggest meconium peritonitis. A fetal echocardiogram can be considered if a detailed cardiac evaluation cannot be performed. 

1)    Idiopathic benign lesion

2)    Infectious causes³:
a.    Toxoplasma Gondii 
b.    Rubella 
c.    Cytomegalovirus (CMV) –most common intrauterine infection
d.    Parvovirus B19 
e.    Varicella Zoster Virus (VZV)
f.    Herpes Simplex Virus (HSV)
g.    Syphilis

3)    Aneuploidy/ Genetic⁴:
a.    Chromosome abnormalities
b.    Cystic fibrosis which is associated with meconium peritonitis 
i.     Meconium peritonitis -likely due to underlying bowel disorder leading to vascular impairment and perforation followed by inflammatory response. Peritoneal calcifications may develop secondary to the inflammatory response and can appear along the edge of the liver.

4)    Vascular insult
a.    Ischemic infarcts
b.    Thromboembolic disease

5)    Space occupying lesions (Both benign and malignant) 

Tumors typically, do not present as small punctate lesions on ultrasound.  Serial ultrasounds to monitor size and to look for development of fetal hydrops can be performed. Tumors which have been reported include⁵: 

• Hemangioma
• Hamartoma 
• Teratoma
• Neuroblastoma 
• Hepatoblastoma 
   

Once hepatic calcifications are identified, and a complete ultrasound examination is performed, the following evaluation can be considered (as locally available):  

1. Testing of maternal blood for syphilis, toxoplasmosis, rubella, cytomegalovirus (CMV), parvovirus B-19, varicella zoster, and herpes simplex viruses. Typically, blood is tested for IgG and IgM antibodies.
2. Amniocentesis can be considered to further evaluate the fetus if viral and/or chromosomal abnormalities are suspected. Tests to consider include karyotype/microarray for chromosome abnormalities and PCR if viruses are suspected.
3. Additional ultrasound examinations throughout the pregnancy to assess fetal size, number of calcifications present and size of calcifications as well as new calcifications in other organ systems.
4.  Delivery at a tertiary care hospital can be considered, especially if a viral or chromosomal abnormality is suspected, or if there are additional anomalies identified. 

Postnatal studies may include: 

1. Liver function tests
2. Viral studies
3. Liver evaluation with ultrasound or X-Ray
4. Dysmorphology evaluation

Further studies are at the discretion of the pediatric provider.  

If the viral evaluation is negative and a chromosomal abnormality is not suspected, the prognosis for an isolated lesion without associated findings is typically excellent. In these cases, an underlying explanation is not typically identified. 
If the lesions appear to grow, or additional lesions are detected in the liver or in other organs, there may be an underlying diagnosis. Lesions which increase in size, are multiple, large, or scattered throughout other organ systems may be due to an infection or chromosomal abnormalities. In these cases, the prognosis depends on the specific etiology. 
 

When no other reason is found to explain a hepatic calcification, the risk of recurrence is quite low. If a genetic reason is identified, consultation with a specialist may be helpful to determine future risk. 

1. McNamara A, Levine D. Intraabdominal fetal echogenic masses: a practical guide to diagnosis and management. Radiographics 2005;25:633-645
2. Simchem MJ, Toi A, Bona M, Alkazaleh F, Ryan G, Chitayat D. Fetal hepatic calcifications: prenatal diagnosis and outcome. Am J Obstet Gynecol 2002;187:1617-22
3. Nyberg DA, MacGahan JP, Pretorious DH, Pilu G, 2003, Diagnostic Imaging of Fetal Anomalies.
4. Hawass ND, El Badawi MG, Fatani JA, Al-Meshari A, Makanjoula D, Edress YB. Foetal hepatic calcification. Pediatr Radiol 1990;20:528-35.
5. Makin, E. Fetal and neonatal liver tumors. Early Human Development , 2010: 86 (10), 637-642.
6. Fleischer AC, Manning FA, Jeanty P, Romero R, 2001, sixth edition, Sonography in obstetrics and gynecology.

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