Pediatric hepatocellular carcinoma

Abstract

Pediatric hepatocellular carcinoma (HCC) is the second common malignant liver tumor in children after hepatoblastoma. It differs from the adult HCC in the etiological predisposition, biological behavior and lower frequency of cirrhosis. Perinatally acquired hepatitis-B virus, hepatorenal tyrosinemia, progressive familial intrahepatic cholestasis, glycogen storage disease, Alagille’s syndrome and congenital portosystemic shunts are important predisposing factors. Majority of children (87%) are older than 5 years of age. Following mass immunization against hepatitis-B, there has been a drastic fall in the incidence of new cases of pediatric HCC in the Asia-Pacific region. Management is targeted on complete surgical removal either by resection or liver transplantation. There is a trend towards improving survival of children transplanted for HCC beyond Milan criteria. Chemotherapeutic regimens do not offer good results but may be helpful for down-staging of advanced HCC. Surveillance of children with chronic liver diseases with ultrasound and alpha-fetoprotein may be helpful in timely detection, intervention and overall improvement in outcome of HCC.

Mutational spectrum of Mexican patients with tyrosinemia type 1: In silico modeling and predicted pathogenic effect of a novel missense FAH variant

“…Although we observed a predominance of chronic presentation of the disease (4/8, 50%), we should not discount the possibility of acute forms, as these are not readily detected clinically, and patients may die without diagnosis. The high proportion of hepatocellular carcinoma observed in our patients (5/8, 62.5%) is within the incidence previously reported for this complication in nontreated or late‐treated patients (14%–75%) (Khanna & Verma, ). A conclusive explanation for the hepatocellular carcinoma pathogenesis in HT1 has not been established, it is known that fumarylacetoacetate, maleylacetoacetate, and SA form glutathione adducts that can promote free radical damage of hepatocytes and susceptibility to genotoxicity (Chinsky et al, ).…”

“…Furthermore, fumarylacetoacetate inhibits DNA glycosylases, which play a role in the repair of mutagenic oxidative base lesions in DNA, (Bliksrud, Ellingsen, & Bjørås, ) and explains the high incidence of hepatocellular carcinoma seen in HT1 patients. Early nitisinone treatment has been found to reduce the incidence of hepatocellular carcinoma (Khanna & Verma, ). In the present study, the patient in whom HT1 was detected at an early stage was promptly treated with nitisinone and showed a positive 1‐year outcome, which is consistent with the successful experiences reported worldwide (Alvarez & Mitchell ).…”

Animal Modeling of Pediatric Liver Cancer

“…To be clear, pediatric and adult HCC differ greatly, including in their etiological predisposition and biological behavior, and, therefore, require unique mouse models for meaningful research. HCC in adults usually occurs after chronic necro-inflammation has been ongoing for many years due to alcohol consumption, viral hepatitis, or non-alcoholic fatty liver disease [60]. On the other hand, pediatric HCC develops spontaneously or in the setting of underlying cirrhosis or metabolic, infectious, or vascular liver disease [60].…”

“…HCC in adults usually occurs after chronic necro-inflammation has been ongoing for many years due to alcohol consumption, viral hepatitis, or non-alcoholic fatty liver disease [60]. On the other hand, pediatric HCC develops spontaneously or in the setting of underlying cirrhosis or metabolic, infectious, or vascular liver disease [60]. Notably, survival of children with HCC has improved drastically over the last 30 years, with some patients even responding to chemotherapy while adults with similar severity of disease have worse survival rates [60].…”

“…On the other hand, pediatric HCC develops spontaneously or in the setting of underlying cirrhosis or metabolic, infectious, or vascular liver disease [60]. Notably, survival of children with HCC has improved drastically over the last 30 years, with some patients even responding to chemotherapy while adults with similar severity of disease have worse survival rates [60].…”