Hepatocellular Carcinoma Risk in Hepatitis C Stage-3 Fibrosis After Sustained Virological Response With Direct-acting Antivirals

María Sánchez-Azofra; Inmaculada Fernández; María L. García-Buey; Lourdes Domínguez-Domínguez; Conrado M. Fernández-Rodríguez; Antonio Mancebo; Lucía Bonet; Pablo Ryan; Francisco Gea; Antonio Díaz-Sánchez; Marian García-Mayor; Luz Martín-Carbonero; Pilar Castillo; María L. Manzano; Leticia González-Moreno; Federico Pulido; María L. Gutiérrez; José M. Moreno; Irene M. García-Amengual; Guillermo Cuevas; Antonio Guerrero; Miguel Rivero-Fernández; María E. Portales; María L. Montes; Antonio Olveira

Disclosures

Liver International. 2021;41(12):2885-2891. 

In This Article

Results

The initial study population comprised 850 patients with TE values of 9.5–14.5 kPa who started treatment with DAA between January and December 2015. Of these, 344 (40.5%) were excluded (Figure 1). The final sample eligible for analysis comprised 506 patients. Their main characteristics are summarised in Table 1.

Figure 1.

Patient flowchart. F3, stage 3 liver fibrosis; DAA, direct-acting antivirals; SVR, sustained virological response; HCC, hepatocellular carcinoma; IFN, interferon

Median follow-up was 33.7 (22.1–39.1) months. During this period, a total of 1611 abdominal ultrasounds were performed. The median time between abdominal ultrasounds was 8.1 (6.5–11.9) months. Adherence to the screening program was 75% (ratio between expected and performed abdominal ultrasounds, 0.5–1.00). Follow-up was completely retrospective in only 17.8% of the cohort and ambispective in 82.2%.

Six liver tumours were diagnosed during the study period: 5 HCC and 1 intrahepatic cholangiocarcinoma (Table 2). The median time between the SVR and the diagnosis of primary liver tumour was 29.4 months (26.8–39.3). The baseline TE was below 12 kPa in all cases. The TE score at diagnosis of HCC was available in 4 cases. An increase in the TE value was observed in the patient diagnosed with cholangiocarcinoma (TE 17 kPa), whose alcohol intake was significantly high. The TE of the remaining cases remained below the baseline value at the diagnosis of HCC. The baseline value of the FIB-4 score (before treatment) was below 3.25 in all cases. No progression of the FIB-4 score was observed after treatment, and the value remained below 3.25 at the diagnosis of tumour in all cases. The cumulative incidence of the primary liver tumour was 2.9% (95% CI: 0–5.6) at 60 months (Figure 2); the incidence rate was 0.47 per 100 patients per year (95% CI: 0.17–1.01). The univariate analysis did not reveal an association between any of the variables and PLT (Table 3). When the combined variable male and age >55 years was included in the multivariate analysis and adjusted for HIV, hyperlipidaemia, diabetes mellitus, alcohol consumption, genotype 3 and baseline elastography value, it was significantly associated with a higher risk of primary liver tumour (HR 7.2; P = .029; Table 3), with a specific incidence rate of 1.10 per 100 patient-years (95% CI: 0.30–2.81). An analysis of the cohort comprising only HCV-monoinfected patients revealed no differences with the sample as a whole (data not shown).

Figure 2.

Cumulative probability of primary liver tumour. HCC, hepatocellular carcinoma

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