Hepatic hemangiomas are considered to be the most common benign tumors of the liver. They are often found incidentally while investigating for other causes of liver disease. Hemangiomas that are less than 10 cm are not expected to cause any problems. Typically, they do not enlarge and, apart from regular follow-up, no definitive treatment is indicated. This is a posthumous case report of a male child with a medium-sized hemangioma from infancy, complicated by cryptogenic cirrhosis and hepatopulmonary syndrome. It demonstrates the challenges of managing a child with such complicated conditions in a resource-limited setting.
An 8-month-old boy was admitted to the Paediatric Ward of Princess Marina Hospital (PMH), the main government referral hospital in Botswana, with abdominal distention and nonbile-stained, nonprojectile vomiting for 2 weeks. No fever, irritability, diarrhoea, or poor feeding was reported. The child was born at term by uncomplicated spontaneous vaginal delivery to a mother who was already on highly active antiretroviral therapy (HAART) before pregnancy. His birth weight was 2950 g. The patient was enrolled into the Perinatal Mother-to-Child Transmission programme as per Botswana guidelines [
The child was previously admitted to PMH when he was 3 months old with culture-negative sepsis and received empiric intravenous antibiotics. On examination during an admission at the age of 8 months, he was slightly lethargic with dry mucus membranes and a capillary refill time of less than 2 seconds. The anterior fontanelle was slightly sunken. Oxygen saturation in room air was 99%. Vital signs and anthropometric measurements were within normal limits. There was no respiratory distress or dysmorphic features. In addition, the patient had mild scleral icterus. The abdomen was distended and soft; however, an irregular and nontender hepatomegaly of 6 cm was palpable below the right subcostal margin, with no splenomegaly. The rest of the physical examination was unremarkable.
Full blood count showed mild leukocytosis and normocytic anemia, whilst liver function tests demonstrated a mild transaminitis. Renal function tests showed raised creatinine and urea consistent with dehydration. Serum electrolytes and thyroid function tests were normal. Hepatitis virus serology was negative (Table
Laboratory results.
Age | 8 m | 4 y |
---|---|---|
FBCa | ||
WBC (5−10 × 103/mL) | 12 | 8 |
Neutrophils (40−60%) | 68 | 42 |
Lymphocytes (20−40%) | 31 | 28 |
Hb (11.5−14 g/dL) | 10 | 17.1 |
MCV (75−90 fL) | 88 | 67.5 |
Platelets (145−450 × 103/mL) | 470 | 100 |
LFTsb | ||
Total bilirubin (<17.1 |
0.8 | 0.53 |
Total protein (63−80 mg/dL) | 76.3 | 71.7 |
Albumin 35−55 mg/dL | 34.5 | 33 |
ALP (50−160 IU/L) | 257.8 | 262 |
ALT (0−30 IU/L) | 78 | 75.4 |
AST (0−40 IU/L) | 86.3 | 84 |
GGT (0−30 IU/L) | 63.6 | 69 |
LDH (140−280 IU/L) | 220 | 262 |
U and Ec | ||
Na (135−145 mmol/L) | 142 | — |
K (3.5−5.5 mmol/L) | 3.8 | — |
Cl (98−106 mmol/L) | 101 | — |
Urea (7–14 mmol/L) | 22 | — |
Creatinine (88−176 |
83.7 | — |
TFTsd | ||
FT4 (3.5−6.5 |
3.78 | — |
T3 (11.5−22.7 ng/dL) | 20.13 | — |
TSH (0.35−5.5 |
4.81 | — |
Coagulation | ||
aPTT (30−45 s) | 35 | 30.6 |
INR (0.8−1.2) | 0.97 | 1.13 |
Serum serology studies | ||
Hepatitis A and B viruses | Negative | Negative |
Autoimmune screen | ||
ANAs | — | Negative |
Serum immunoglobulins | — | Normal |
aFull blood count; bliver function tests; curea and electrolytes; dthyroid function tests.
Abdominal ultrasound showed hepatomegaly (5 cm × 5 cm × 5 cm) with mild ascites. The spleen, gallbladder, pancreas, kidneys, aorta, and inferior vena cava were normal. There was no retroperitoneal lymphadenopathy. Magnetic resonance imaging scan of the abdomen 3 months later showed mild hepatomegaly with a large well-encapsulated exophytic lesion (5 cm × 5 cm × 5.3 cm) in the left lobe of the liver consistent with hemangioma. He was started on propranolol therapy to treat the hemangioma. Between the age of 1 and 4 years, he had several abdominal ultrasound scans, and all showed that the liver mass remained the same size.
At the age of 4 years, he was growing well, with weight plotting consistently above 0 Z-score weight-for-age. Developmental milestones were appropriate for age. However, for the first time, he was noted to be cyanosed, both peripherally and centrally, with oxygen saturation of 70% in room air, improving to 85% with supplemental oxygen by nasal prongs. He had developed conjunctival chemosis and finger clubbing (Figure
(a) Weight-for-age plot for the patient. Growth consistently above 0 Z-score (middle line on the image) throughout the under-five period. (b) Central cyanosis (arrow). (c) Finger clubbing (arrows).
Of note on the full blood count were polycythemia, microcytosis, and thrombocytopenia, with a hemoglobin of 17.1 g/dL, mean corpuscular volume of 67.5 fL, and platelet count of 100 × 109/L. Liver function tests showed no significant changes from previous. Coagulation profile was normal (Table
With these examination and laboratory findings, we strongly suspected hepatopulmonary syndrome although he had no overt clinical signs of hepatic cirrhosis. We thought that he had developed portal hypertension, which could explain the splenomegaly and the thrombocytopenia. He was referred to a hepatobiliary specialist in South Africa, where computed tomographic scan of the abdomen and pelvis showed a large mass in segment III of the left lobe of the liver (4.98 × 4.51 cm), that was suggestive of hemangioma, and had not changed in size over the years (Figure
(a) CT scan of the abdomen. Note the hepatic hemangioma (crossed lines 1 and 2). (b) Liver histology. Left to right: Liver parenchyma is present which, although subcapsular, shows evidence of marked distortion of the normal architecture, with fibrosis present surrounding regenerative-type nodules. Masson trichome stain shows extensive interstitial fibrosis surrounding regenerative-type nodules, as can be appreciated on the microphotograph. Reticulin stain shows twinning of the cell plates, which can be appreciated on the microphotograph.
Transesophageal echocardiography showed an anatomically normal heart with normal valves, normal chamber size and function, and no intracardiac shunts (patent foramen ovale or septal defects). The internal diameters for the left ventricle were 42.7 mm (diastolic) and 28.1 mm (systolic). Ejection fraction was 64% (normal). Shortening fraction was 34% (normal). All major vessels were of normal diameter (inferior vena cava: 5.52 mm; right pulmonary artery: 8.32 mm; main pulmonary artery: 15.19 mm; aorta: 22.63 mm). There were no features of pulmonary hypertension. Contrast enhancement with saline showed a delayed opacification of the left atrium (positive bubble test), suggesting an intrapulmonary right-to-left shunt most probably due to pulmonary vascular dilatation. The PaO2 was <34 mmHg, and oxygen saturation in room air was 65% (80% on nasal oxygen).
Exploration with a view to resection of the liver lesion revealed no mass. Instead, advanced cirrhosis was noted.
A wedge liver biopsy showed grossly distorted architecture with regenerative micronodules of hepatocytes surrounded by dense fibrotic septa showing portoportal and portovenous linkage (Figure
All other studies, including hepatitis virus serology, autoimmune screen, and copper studies, were also negative. The patient was assessed as having cryptogenic cirrhosis and severe hepatopulmonary syndrome (in view of chronic liver disease, chronic hypoxia, and the delayed opacification saline bubble test). He was assessed in the liver transplant unit and was considered to be a candidate for liver transplantation. However, in view of the severity of the hepatopulmonary syndrome, he was put on home oxygen to try and prevent his pulmonary status from deteriorating and improve his arterial oxygen content. He was advised to return 2 months later when he would be worked up for liver transplantation. Sadly, he was unable to return to South Africa for his next appointment due to financial constraints. He was on home oxygen until his demise. An autopsy was offered, but the parents declined to have it done.
Hepatic hemangiomas are considered the most common benign tumors of the liver. They are often found incidentally while investigating for other causes of liver disease. They are classified according to their size into capillary (less than 3 cm in greatest diameter), medium (between 3 cm and 10 cm), and giant or cavernous (more than 10 cm) [
Various treatment options for hemangiomas have been described in the literature. These include the use of drugs like corticosteroids, interferon-
Hepatopulmonary syndrome is a well-recognized pulmonary complication of liver cirrhosis. It is usually diagnosed in the presence of a triad of liver disease, oxygenation defect, and intrapulmonary microvascular dilatations [
Dyspnea has both positive and negative predictive values of 100% for hepatopulmonary syndrome. Cyanosis has a negative predictive value of 97% while finger clubbing has been reported to have a negative predictive value of up to 75% [
Hepatopulmonary syndrome is classified as mild (PaO2 ≥ 80 mmHg), moderate (PaO2 ≥ 60 < 80 mmHg), severe (PaO2 ≥ 50 < 60 mmHg) and very severe (PaO2 < 50 mmHg). These patients consistently have elevated serum levels of nitric oxide and carboxyhemoglobin, both of which have been postulated to play a role in the pathogenesis of the syndrome [
In infancy, biliary atresia and genetic metabolic disease are the commonest cause of chronic liver disease, while chronic viral hepatitis and autoimmune disease predominate after infancy. Cryptogenic cirrhosis accounts for 5–15% overall [
The patient had two admissions in infancy due to severe illnesses. We did not find their aetiology, and investigations did not point towards immunodeficiency. However, we are also aware that HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life [
Liver transplantation is the only successful treatment for hepatopulmonary syndrome [
Our case report, the first of its kind to be reported from Botswana, demonstrates the difficult challenges of managing a child with cryptogenic cirrhosis and hepatopulmonary syndrome in the setting of liver transplant considerations.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
The authors would like to sincerely thank the parents of the child for providing informed consent to publish the case (including the images of the child) in this case report.