Discussion
In our institution, we have over 120 patients receiving SCT against
hematological malignancies and solid tumors in childhood, adolescence or
young adulthood so far. However, we have encountered only two patients
that developed hepatic cirrhosis after SCT, and both suffered from
neuroblastoma. Neither case showed evidence of hepatitis virus infection
including hepatitis C virus (HCV), which has been accepted as the most
frequent cause of cirrhosis 1)4). Treatment,
conditioning before SCT and other characteristics of our two cases
differed markedly from each other except for the underlying disease,
neuroblastoma. Speculation on the involvement of the underlying disease
in the onset of cirrhosis is thus natural. The liver is known as an
organ to which neuroblastoma frequently metastasizes, and a previous
report showed that the frequency of neuroblastoma metastasis to the
liver at the time of diagnosis was 29.6% 5). However,
since very few patients undergo liver biopsy at diagnosis or during
treatment, and evaluation is usually made only by imaging, the exact
frequency of liver involvement remains unclear. Another speculation
regarding underlying condition is that some congenital predisposition
(such as DNA repair defects, telomere disorders and so on) and
autoimmunity had some impact on massive hepatic damage. Both our cases
had no medical history, family history or congenital malformations that
suspected them. Other possible causes of cirrhosis would be TBI,
VOD/SOS, GVHD, CMV infection and iron overload. Regarding TBI, a
previous report showed that radiation-induced liver disease is unlikely
to occur after a mean liver dose around 30 Gy in conventional
fractionation 6). Neither case was exposed to 30 Gy at
the liver in our patients. Liver damage associated with VOD/SOS1), GVHD 7), CMV infection8) and iron overload 9) could
conceivably have contributed to the onset of cirrhosis. In our cases,
however, these conditions would not play a direct inducer of hepatic
cirrhosis since these were properly handled by medications and achieved
clinical improvement. We have made a number of considerations on the
causes or mechanisms that induced hepatic cirrhosis in our two patients
but could not get any definitive conclusion.
To the best of our knowledge, this report represents the first of
hepatic cirrhosis after SCT against neuroblastoma. Since high-risk
neuroblastoma could metastasize to various organs including the liver
and requires multidisciplinary treatment, various severe complications
can occur. Our cases demonstrated that hepatic cirrhosis could develop
at any time after treatment for neuroblastoma including SCT, and careful
life-long monitoring of the liver is warranted to detect cirrhotic
events before progression to hepatic failure.