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.