RESULTS

Study selection and characteristics

Figure 1 reports the search strategy used in this meta-analysis. Thirty-four9–42 studies published between 2003 and 2017 were analyzed. They included 11,216 HCC patients treated with RFA. The characteristics of the study are gathered in Table 1.


Continue Reading

 


(To view a larger version of Table 1, click here.)

Overall survival

The analysis of liver functionality showed that Child–Pugh B vs Child–Pugh A (HR =2.32; 95% CI: 2.201–2.69; P<0.0001) (Figure 2A), increase in bilirubin (HR =1.03; 95% CI: 1.01–1.04; P<0.0001) (Figure 2B), presence of Portosystemic collaterals (HR =1.54; 95% CI: 1.31–1.82; P<0.0001) (Figure 2C), and albumin-bilirubin (ALBI) score 1 vs 0 (HR =2.69; 95% CI: 2.10–3.44; P<0.0001) (Figure 2D) were predictive of poor OS. Decrease in prothrombin activity (HR =0.97; 95% CI: 0.96–0.99;P<0.0001) (Figure 2E) and increase in albumin (HR =0.90; 95% CI: 0.87–0.94; P<0.0001) (Figure 2F) were predictive of better OS.

(To view a larger version of Figure 2, click here.)

Tumor size was not predictive of OS (HR =1.01; 95% CI: 0.99–1.03; P=0.269) (Figure 3A) when considered as a continuous variable. Yet, it was predictive of OS when considered as a cutoff value. An either size cutoff of 2 or 3 cm was predictive of poor OS (>2 cm, HR =1.41; 95% CI: 1.23–1.61;P<0.0001, Figure 3B; >3 cm, HR =1.43; 95% CI: 1.17–1.74; P<0.0001, Figure 3C). When considering the number of nodules, the presence of >1 nodules (HR =1.59; 95% CI: 1.46–1.74;P<0.0001) (Figure 3D) was predictive of poor OS.

(To view a larger version of Figure 3, click here.)

Gender was not predictive of OS (male vs female HR =1.07; 95% CI: 0.99–1.15; P=0.091) (Figure S1A; see original article), while an older age (HR =1.02; 95% CI: 1.01–1.03; P<0.0001) (Figure S1B) and an age >65 years (HR =1.73; 95% CI: 1.40–2.12; P<0.0001) (Figure S1C) were predictive of poor OS.

Data showed that an alpha-fetoprotein cutoff of 20 ng/mL (>20 ng/mL vs <20 ng/mL HR =1.46; 95% CI: 1.25–1.70; P<0.0001) (Figure 4A) was predictive of poor prognosis, whereas alpha-fetoprotein cutoffs of 200 ng/mL (>200 ng/mL vs <200 ng/mL HR =1.21; 95% CI: 0.74–1.95; P 0.475) (Figure 4B) and 400 ng/mL (>400 ng/mL vs <400 ng/mL HR =1.30; 95% CI: 0.91–1.85; P 0.332) (Figure 4C) were not predictive of poor prognosis.

(To view a larger version of Figure 4, click here.)

As for etiology, data show that hepatitis B virus (HBV) infection (HBV infection vs no HBV infection HR =0.86; 95% CI: 0.77–0.97; P 0.011) (Figure 5A) was predictive of good prognosis, whereas patients with hepatitis C virus (HCV) infection vs patients without HCV infection showed no statistically significant difference (HR =1.14; 95% CI: 0.95–1.36; P 0.147) (Figure 5B).

(To view a larger version of Figure 5, click here.)

Finally, neutrophil–lymphocyte ratio (NLR) was predictive of poor prognosis (high vs low HR =1.91; 95% CI: 1.35–2.70; P<0.0001) (Figure S1D; see original article).

Recurrence-free survival

The analysis of liver functionality showed that only Child–Pugh B vs Child–Pugh A was predictive of poor RFS (HR =1.24; 95% CI: 1.11–1.40; P<0.0001) (Figure 6A). Bilirubin, albumin, prothrombin activity, and portosystemic collaterals were not predictive of RFS (Figure S2A–D).

(To view a larger version of Figure 6, click here.)

Tumor size was not predictive of RFS when the size of the nodule was considered as a continuous variable (HR =1.00; 95% CI: 0.99–1.01; P 0.465) (Figure 6B). Yet, when the cutoff was considered, tumor sizes >2 cm vs <2 cm (HR =1.77; 95% CI: 1.47–2.12; P<0.0001) (Figure 6C) and >3 cm vs <3 cm (HR =1.31; 95% CI: 1.13–1.53; P<0.0001) (Figure 6D) were predictive of poor RFS. When considering the number of nodules, the presence of >1 nodule (HR =1.62; 95% CI: 1.47–1.78;P<0.0001) (Figure 6E) was predictive of poor RFS.

Gender was not predictive of RFS (male vs female HR =1.05; 95% CI: 0.96–1.15; P 0.243) (Figure S2E; see original article), whereas an older age (HR =1.01, 95% CI: 1.00–1.01; P 0.021) (Figure S2F) was predictive of poor RFS.

Data showed that an alpha-fetoprotein cutoff of 400 ng/mL (>400 ng/mL vs <400 ng/mL HR =1.16; 95% CI: 0.93–1.46; P 0.186) (Figure 6F) was not predictive of RFS.

As for etiology, HBV infection (HBV infection vs no HBV infection HR =1.16; 95% CI: 1.03–1.31; P0.012) (Figure 7A) was predictive of poor RFS. The presence of HCV infection vs no HCV infection (HR =1.15, 95% CI: 1.04–1.27; P 0.008) (Figure 7B) was predictive of poor RFS.

(To view a larger version of Figure 7, click here.)

Finally, NLR was not predictive of RFS (high vs low HR =1.28; 95% CI: 0.98–1.69; P 0.075).