The Impact of HCV Eradication by Direct-acting Antivirals on the Transition of Precancerous Hepatic Nodules to HCC

A Prospective Observational Study

Hidenori Toyoda; Takashi Kumada; Toshifumi Tada; Kazuyuki Mizuno; Yasuhiro Sone; Tomoyuki Akita; Junko Tanaka; Philip J. Johnson

Disclosures

Liver International. 2019;39(3):448-454. 

In This Article

Results

Baseline Characteristics of Study Patients

Table 1 shows the characteristics of the study patients. The presence of cirrhosis was defined clinically by the presence of oesophageal/gastric varices, collateral veins due to portal hypertension, or splenomegaly and was observed in 112 patients (27.9%). NHHNs were detected in 35 patients (8.7%) by EOB-MRI before DAA therapy. The size of NHHNs was 8.5 (3-19) mm. SVR was achieved in 383 patients (95.5%) by DAA therapy. NHHNs were detected at baseline in 33 of 383 patients (8.6%) who achieved SVR and two of 18 patients (11.1%) who failed to achieve SVR.

Hypervascularization of Baseline NHHNs and Emergence of new NHHNs After the Eradication of HCV

Patients were followed up for 12.7 ± 4.6 months (median, 13.6 months) after SVR. No patients were lost to follow-up. Typical hypervascular HCC developed in six patients after DAA therapy: five patients who achieved SVR and one patient who failed to achieve SVR. HCC developed in three of 190 patients (1.58%) who underwent daclatasvir + asunaprevir for 24 weeks (including one patient with failure of SVR), one of 96 patients (1.04%) who underwent sofosbuvir + ledipasvir for 12 weeks, and two of 115 patients (1.74%) who underwent sofosbuvir + ribavirin for 12 weeks.

Among 383 patients who achieved SVR, 33 had NHHNs detected before DAA therapy. Hypervascularization of NHHNs was observed in five of 33 patients (15.2%, Figure S1, Table 2a). All of these liver nodules were confirmed as typical hypervascular HCC by dynamic enhanced computed tomography and angiography after EOB-MRI. All patients underwent hepatic resection, and HCC was confirmed histologically based on the resected specimens. The resected HCCs were well-differentiated in three patients and were moderately differentiated in the remaining two patients. All but one had histologically confirmed cirrhosis at resection. The sizes of NHHNs at baseline were 3 to 16 mm, and increased at hypervascularization except in one patient. In one patient, one of two NHHNs showed hypervascularization.

Among the 350 patients in whom NHHNs were not detected at baseline and who achieved SVR, eight patients (2.3%) demonstrated the new development of such nodules (Figure S2). No hypervascular typical HCCs were detected in these 350 patients.

Supplementary Figure 1.

Supplementary Figure 2.

Hypervascularization Rates of NHHNs in Patients With HCV Eradication vs Patients With Persistent HCV Infection: Propensity Score-matched Comparison Among Patients With NHHNs at Baseline

Among patients who had NHHNs at baseline, propensity score matching was used to compare the incidence of hypervascularization of NHHNs in patients who achieved SVR with that in patients with persistent HCV infection. Thirty-three patients with persistent HCV infection were selected as matched controls. As shown in Table S1, there were no significant differences in the characteristics of patients who achieved SVR and those who did not. In the control patients, typical hypervascular HCC developed in eight patients in the observation period (Table 2b).

Figure 3 and Figure S3 compare the incidence and time interval of the transition from NHHNs to typical hypervascular HCC in patients who achieved SVR and those with persistent HCV infection. Follow-up EOB-MRI studies began at approximately 6 months after baseline. There was no significant difference in the incidence of hypervascularization at 12, 18 and 24 months between those who did achieve SVR (11.8%, 24.2% and 25.2%) and those with persistent HCV infection (9.1%, 15.2%, and 24.9%) respectively (P = 0.6170).

Figure 3.

Hypervascularization rates of non-hypervascular hypointense nodules in patients with HCV eradication by DAA therapy vs patients with persistent HCV infection: propensity score-matched comparison among patients with non-hypervascular hypointense nodules at baseline. No difference was observed between the two groups. Horizontal axis, period after baseline (mo). Red line, patients with HCV eradication. Blue line, patients with persistent HCV infection

Supplementary Figure 3.

Emergence of NHHNs in Patients With HCV Eradication and Patients With Persistent HCV Infection: Propensity Score-matched Comparison Among Patients Without NHHNs at Baseline

Among patients who did not have NHHNs at baseline, propensity score matching was used to compare the incidence of the emergence of new NHHNs in patients who achieved SVR with that in patients with persistent HCV infection (control subjects). One hundred and thirty-nine patients were compared with matched controls. As shown in Table S2, there were no significant differences in the characteristics of patients who achieved SVR and those of the controls.

Figure 4 compares the incidence of the emergence of NHHNs between patients who achieved SVR and those with persistent HCV infection. Follow-up EOB-MRI studies began at 6 months after baseline. The incidences of the emergence of these nodules at 12, 18 and 24 months were 3.4%, 3.4% and 10.3% in patients with SVR, and 5.2%, 5.2% and 8.9% in patients with persistent HCV infection respectively. The incidences did not differ between two groups (P = 0.7282).

Figure 4.

Rates of the emergence of non-hypervascular hypointense nodules in patients with HCV eradication by DAA therapy and patients with persistent HCV infection: propensity score-matched comparison among patients without non-hypervascular hypointense nodules at baseline. No difference was observed between the two groups. Horizontal axis, period after baseline (mo). Red line, patients with HCV eradication. Blue line, patients with persistent HCV infection

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