In recent years, with the continuous improvement of diagnosis and treatment, the prognosis of HB has been greatly improved. The research led by Einar Hafberg [9] showed that the current 5-year overall survival rate of HB children had reached 75%, and the 5-year EFS had also reached about 65–70%. In this paper, HB was investigated for infants under 1 year old (median age 8.40 months). The median follow-up time was 58 months. The results showed that the 5-year overall survival rate was 80.1% and the event-free survival rate was 77.5%, both of which were higher than those reported in the literature, suggesting that infants with HB had a relatively good prognosis.
Some scholars had studied children with HB found in pregnancy and diagnosed after birth, and found that children with low birth weight, especially those with a weight less than 1000 g, were more likely to develop HB in the future [10]. Other studies had shown that factors such as advanced maternal age, hypertension during pregnancy, excessive weight, excessive amniotic fluid, and a history of smoking all increased the incidence of HB [11–12]. The three HB patients found during pregnancy in this study were all low birth weight infants, and there were risk factors such as advanced maternal age, maternal hypertension and smoking history, which were consistent with the views of foreign scholars. In this data, 6 IVF (in-vitro fertilization) infants were also diagnosed with HB in infancy, and 3 of them were fraternal twins. Although there are no studies to prove that IVF, twin or multiple pregnancy may increase the prevalence of HB, it is important to note that the pregnant state is easy to cause fetal hydramnios and increase the risk of pregnancy complications, these factors could increase the test-tube baby and multiple birth’s probability of developing HB.
Studies had shown that [13], peripheral platelet count may increase when patients getting infected or having malignant tumors and some chronic diseases. More than half (56.8%) of the cases in this data have elevated platelets. However, through risk factor analysis, whether the platelets will increase is not significantly related to the prognosis of infant HB, it is not consistent with the report above, and this may because the cases are very few. AFP is a special protein in the blood produced by the liver. At present, domestic and foreign experts had reached a consensus that AFP was an important tumor marker of HB. Not only the level of its initial diagnosis was important for prognosis judgment, but also it was always an important indicator for observation of therapeutic effects in the treatment process. Scholars such as Meyers RL had suggested that low levels of AFP at the initial diagnosis were indicators of poor prognosis [14]. The results of this study showed that the AFP of infant HB was mostly high at the initial diagnosis, and the prognosis was relatively good; while the prognosis of cases with AFP < 1210 ng/ml was poor, consistent with relevant foreign reports. Such children are often insensitive to chemotherapy and easy to relapse, resulting in shortened survival period. It should be noted that some normal full-term newborns may also have increased AFP, which needs to be distinguished from HB in the neonatal period, but the former falls to the normal range more than 2–3 months after birth. HCG is secreted and synthesized by the trophoblast cells of the placenta, and can stimulate the testes of the fetus to secrete testosterone to promote male differentiation [15]. In rare cases, HB tumor cells can secrete hCG, which leads to precocious puberty and is more common in boys. Malati T [16] believes that increased secretion of hCG is not a common phenomenon of HB, and its level has no clear relationship with the prognosis of HB, and the occurrence of precocious puberty is rare. At present, domestic and international reports of precocious puberty caused by hCG are mainly based on case reports. The case of HB in our center with premature puberty caused by elevated hCG was a boy. After comprehensive treatment, the hCG progressively decreased, suggesting that the level of hCG might become another important biological marker of HB after AFP. However, a large sample of clinical data is needed for subsequent research and verification.
Compared with older children, HB in infancy is dominated by pure fetal type with relatively good differentiation [17]. Through statistical analysis of big data, Piotr Czauderna [18] concluded that complete fetal HB had a better event-free survival time than other pathological types, and small cell undifferentiated type was considered to be an important negative factor to affect prognosis. According to the distribution of pathological tissues in this study, epithelial type was dominant in infant HB, and the fetal type with good prognosis was the most in the epithelial type, which was consistent with the literature reports. Although the final statistical results of this study did not support the correlation between pathological classifications and prognosis (P > 0.05), 2 children with small cell undifferentiated type all died finally in this group of data. According to a retrospective study, SIOPEL believes that the PRETEXT stage can predict the resectability of the tumor to a certain extent [19], which is important for the prognosis either. Because the complete resection of liver tumors is the key to treatment for HB children. The data in this group showed that the EFS of patients with PRETEXT stage IV was significantly lower than that of children with other stages. It also confirmed that PRETEXT stage was significantly related to prognosis.
Infant HB can have systemic metastasis early in the course of the disease. Like older HB children, the lung is the most common metastatic site, mostly from blood transfer, and it is likely to occur in the lung margin or terminal vascular supply area [20], and nodular shadow of extrapulmonary zone can be seen in imaging. In the 45 cases of distant metastasis in this study, 86.7% had lung metastasis, which is consistent with literature reports. Other metastatic sites can also be found in brain, bone, etc. It is worth mentioning that there was one case of HB with right atrial tumor thrombus in this data. It is very difficult for the tumor cells to form a tumor thrombus in heart blood vessels where blood flows very fast, so this was a rare case in China. Unfortunately, despite receiving active treatment, the patient eventually died of ventricular fibrillation due to the shedding of atrial tumor thrombus. Because much more blood flows in the liver, HB is prone to intrahepatic metastasis, forming multiple liver lesions and venous tumor thrombus. If it is not clear, it is prone to tumor recurrence and distant dissemination. The results of this study showed that the prognoses of HB with distant metastases and multiple liver lesions were relatively poor, which were consistent with literature reports [21].
Infant HB is sensitive to chemotherapy [22]. Although multidisciplinary treatments such as surgery, interventional therapy, targeted therapy and immunotherapy are gradually developed, surgical resection combined with chemotherapy is still the main treatment option. Preoperative chemotherapy can effectively shrink the tumor to create an opportunity for complete surgery to remove the tumor. Postoperative consolidation chemotherapy can effectively prevent the recurrence of residual tumor and improve the cure rate. The patients in this group mainly used chemotherapy combined with surgical treatment. Individualized chemotherapy was adopted for high-risk cases of recurrence, distant metastasis, tumor thrombus invasion and refractory, and achieved good clinical efficacy. According to the WHO classification criteria for toxicity of chemotherapy, the systemic toxic and side effects of chemotherapy for infants with HB in this data are mainly concentrated in grade II, and the proportion of grade IV is not high. This may be related to the body's strong metabolism regeneration ability, and good tolerance to chemotherapy drugs in infant. It can also be seen that the chemotherapy regimen in this study is safe. However, because infants are young, the organs are imperfectly developed, and chemotherapy drugs can cause organ damage (especially platinum drugs can cause liver and kidney function and hearing damage, anthracycline drugs can cause heart damage) and even the risk of secondary tumors, it is necessary to regularly evaluate organ functions to ensure the safety of medication. For children with refractory HB, high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) can also be used. Our center had treated APBSCT for a 3-year-old HB patient, which had significantly prolonged the survival time of the child, but it had not yet been carried out in infant HB. I look forward to the next treatment in infant HB. In recent years, liver transplantation had been successful in treating unresectable or PRETEXT IV HB children, and there were reports in the literature that its 5-year survival rate was close to 85% [23]. In this study, 1 infantile child with HB who had multiple intrahepatic tumor foci was still not effective after conventional surgery, chemotherapy and arterial embolization. Living liver transplantation was performed at the age of 8 months and was successful. After transplantation, the patient underwent consolidation chemotherapy for 2 cycles. Regular reexamination of AFP and imaging showed CR after that.