Is it time to extend criteria for hepatic resection in the treatment of hepatocellular carcinoma?
Authors: Franco Trevisani, Laura Bucci, Francesca Garuti
Journal: Hepatology (2016)

Potential conflict of interest: Dr. Trevisani consults, is on the speakers' bureau, and received grants from Bayer. To the Editor: A large multiregional cohort study showed that the selection criteria proposed by Western guidelines for hepatic resection (HR) in hepatocellular carcinoma can be moderately expanded.1 Namely, HR may be extended to patients with either clinically significant portal hypertension (CSPH; defined as either splenomegaly, varices, or platelet count <100,000/μL but without ascites) or slight hyperbilirubinemia (1.1‐2.0 mg/dL) without compromising outcomes with respect to "ideal" candidates (single tumor, no CSPH, and normal bilirubin). Instead, the combination of both factors yields poorer survival. This study did not compare the short‐term mortality and HR extent among all patient subgroups, and a potential selection bias due to the refusal to submit data by more than half of the enrolling centers cannot be excluded. We therefore tested these "extended criteria" in hepatocellular carcinoma patients resected between 2000 and 2014 at Italian Liver Cancer centers, to depict the results of HR in clinical practice. Inclusion criteria were Child‐Pugh A class, Eastern Cooperative Oncology Group performance status 0‐1, single or multifocal tumors (≤4), no ascites/vascular invasion/metastases, availability of CSPH, bilirubin, and survival data. Survival was calculated using the Kaplan‐Meier method and compared with the log‐rank test. Three hundred and one consecutive patients were enrolled (mean ± standard deviation for age 66.2 ± 9.2 years, 235 males, 271 Eastern Cooperative Oncology Group performance status 0). Etiologies were hepatitis C virus infection (n = 129), alcohol (n = 39), hepatitis B virus infection (n = 32), nonalcoholic fatty liver disease (n = 13), and mutifactorial (n = 88). Tumors showed a mean size of 3.6 ± 2.2 cm and were single in 248 patients. Mean alpha‐fetoprotein was 272 ± 1,843 ng/mL. The resection extent was reported in 256 cases: major resections were performed in 14.2% of ideal, 17.9% of hyperbilirubinemic, 7.3% of CSPH, and 7.1% of CSHP+hyperbilirubinemic patients (P ≥ 0.293). The median follow‐up was 33.5 months (range 15.2‐58.9). Median survival did not significantly change in patients with hyperbilirubinemia alone (125.1 months, 95% confidence interval [CI] 33.3‐216.8) or CSPH alone (100.4 months, 95% CI 69.6‐131.1) with respect to ideal candidates (93.3 months, 95% CI 68.0‐108.7), while CSPH+hyperbilirubinemic patients had a significantly worse prognosis (85.2 months, 95% CI 58.3‐112.1) (mortality hazard ratio = 1.765, 95% CI 1.020‐3.054) (Fig. 1).Figure 1: Long‐term postresection survival by the presence of hyperbilirubinemia alone (A), CSPH alone (B), or both (C). Abbreviation: OS, overall survival.Instead, the 6‐month mortality rate (heavily influenced by the operative risk) was similar in all groups, being 2.2%, 2.0%, 4.3%, and 0.6% in hyperbilirubinemic, CSPH, and CSPH+hyperbilirubinemic patients and in ideal candidates, respectively (P ≥ 0.132 with respect to ideal candidates). In a population including multifocal hepatocellular carcinomas and Eastern Cooperative Oncology Group 1 patients and over a long‐term follow‐up, the Italian Liver Cancer results confirm that (1) HR can be offered to Child‐Pugh A patients with CSPH or bilirubin levels up to 2 mg/dL without compromising the outcome with respect to "ideal" candidates, provided that the resection extent is considered in the decision‐making process, and (2) this is not true for CSPH+hyperbilirubinemic patients, likely due to more advanced cirrhosis. However, this cannot exclude the possibility that HR may remain the best option for some of them.