Treatment and Prognosis of Fibrolamellar Hepatocellular Carcinoma: a Systematic Review of the Recent Literature and Meta-analysis

Abstract

Background Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare disease and current efforts are focused on the prognosis and on the development of efficient and specific treatments. This study aimed to review the latest evidence regarding FL-HCC treatment and prognosis. Methods A systematic review of the literature over the past 10 years regarding FL-HCC, and meta-analysis of 1-, 3-, and 5-year overall survival (OS) comparing FL-HCC and conventional HCC were performed. Results Overall, 1567 articles were screened, of them 21 were selected for the systematic review, and 6 for meta-analysis. Twenty-one studies included a total of 2168 patients with FL-HCC, with a median age ranging from 11 to 56 years. The majority of patients underwent surgical resection or liver transplantation. After a median follow-up ranging from 24 to 58 months, 1-year OS was 67–100% and 5-year OS was 28–65%. A total of 743 patients with FL-HCC and 163,472 with conventional HCC were included in the meta-analysis. There was a significantly improved 1-, 3-, and 5-years OS in the FL-HCC group compared to the conventional HCC group, although high heterogeneity was found. When excluding population-based studies, and including 96 FL-HCC and 221 conventional HCC patients, the heterogeneity was low, and the meta-analysis showed a significantly longer 1-year OS in patients with FL-HCC than conventional HCC; however, there were no differences at 3- and 5-years OS. Conclusions Surgical resection for FL-HCC is currently the only curative treatment available. FL-HCC is plagued by high-recurrence rates and poor long-term outcomes which may be related to the absence of specific treatment for advanced and recurrent disease.

Incidence and survival of pediatric and adult hepatocellular carcinoma, United States, 2001-2020

“…Our study reconciles the results from SIOPEL and those of population-based studies. We found lower risk in pediatric ages within one year of follow-up, but no difference with longer follow up times, possibly due to higher complete resection rate or delayed follow-up in fHCC [32][33][34][35] . While adults with fHCC had better overall survival than adults with other HCCs, the survival benefit persists beyond one year, possibly due to lower resection rates and higher frequency of underlying liver disease in adults compared to children [32][33][34][35] .…”

Treating rare tumors with liver transplantation

“…FLC is a rare cancer that accounts for <1% of primary liver tumors in the United States [38,39 ▪ ]. Patients typically present with vague discomfort, have no underlying liver disease, and are found to have large, hypervascular, well circumscribed masses in the liver with areas of central necrosis [40].…”

“…These tumors have been linked to a 400-kb deletion on chromosome 19, which leads to a functional DNAJB1-PRKACA chimeric transcript that was detected ubiquitously in whole genome sequencing of FLC tumor samples from 10 patients, cited as proof that FLC is a distinct pathological entity from HCC [42]. Alpha-feto-protein (AFP) as a biomarker for FLC is controversial, though a recent meta-analysis by Glavas et al suggested that in eight studies AFP was elevated in 28% of FLC cases [39 ▪ ]. Additionally, AFP elevation was noted to be associated with significantly reduced survival in patients with FLC (median 43 months in those with elevated AFP versus 134 in those with AFPs in the normal range), suggesting that it may be useful in determining biologically aggressive FLC [43].…”

“…Additionally, recurrence rates after resection are high with studies reporting recurrence in 33–100% of resected FLC patients with a median time to recurrence of 10–33 months [46,50–53]. Despite resection being the mainstay of therapy, as many as 50% of FLC patients have unresectable tumors at diagnosis [39 ▪ ].…”

“…Given the state of current evidence, there are no standard MELD exception points available for patients with FLC. There are also ongoing efforts to elucidate the ability of immunotherapy and DNAJB1-PRKACA targeted therapies to treat unresectable FLCs that are beyond transplant criteria [39 ▪ ,55].…”