Journal Information
Vol. 86. Issue 2.
Pages 197-199 (April - June 2021)
Vol. 86. Issue 2.
Pages 197-199 (April - June 2021)
Scientific letter
Open Access
Hepatocellular carcinoma associated with direct-acting antiviral therapy for hepatitis C virus: A report of two cases
Carcinoma hepatocelular asociado con el uso de la terapia antiviral de acción directa para virus de hepatitis C: reporte de dos casos
R. Tapia-Sosaa, F. Hernández-Cabrala, A. Gabuttib, V.M. Páez-Zayasc, I. García-Juáreza,
Corresponding author

Corresponding author at: Vasco de Quiroga 15, Colonia Belisario Domínguez, Sección XVI, C.P. 14080, Mexico City. Tel.: 55 5487 0900.
a Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
b Departamento de Imagenología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
c Departamento de Donación y Trasplantes, Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, Mexico
This item has received

Under a Creative Commons license
Article information
Full Text
Download PDF
Figures (1)
Tables (1)
Table 1. Summary of clinical cases.
Full Text

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm worldwide and hepatitis C virus (HCV) is the leading cause, conditioning a 3 to 7% risk per year in patients with liver cirrhosis (LC).1 In the era of pegylated interferon (PEG-IFN), the sustained virologic response (SVR) was about 50%, and in cirrhotic patients that achieved SVR, the incidence of HCC decreased to 0.5-1% annually.2

The introduction of direct-acting antiviral (DAA) therapy resulted in a reported SVR above 90%, with a positive impact on the course of HCC, reducing the adverse effects in patients with a more advanced disease stage.3 Despite the promising results of DAA therapy, some reports suggest it may increase the risk for HCC occurrence and recurrence,4 hence our decision to present the following 2 cases (Table 1).

Table 1.

Summary of clinical cases.

Case  Age  Sex  HCV genotype  PCR IU/mL  DAA  Treatment duration  SVR  Tumor size  LRT 
66  1b  2,900,000  Sofosbuvir  24 weeks  Yes  7.3 cm segment VII  TAE 
          Ledipasvir        RFA 
74  1b  3,292,886  Sofosbuvir  12 weeks  Yes  1.7 cmsegment VI  RFA 
          Ledipasvir      0.7 cm segment V   

DAA: direct-acting antiviral; F: female; HCV: hepatitis C virus; LRT: locoregional therapy; M: male; PCR: polymerase chain reaction; RFA: radiofrequency ablation; SVR: sustained virologic response; TAE: transarterial embolization.

Case 1

A 66-year-old man was diagnosed with LC secondary to HCV in 2014. A magnetic resonance imaging (MRI) study performed that same year revealed a 7.3 cm lesion in segment VII, displaying typical HCC behavior, for which he underwent transarterial embolization (TAE). In 2015, he again required TAE, after which he had complete radiologic response (CRR) (Fig. 1a-c) and remained under surveillance. In March 2017, the patient achieved SVR with DAA therapy. A control imaging study performed after SVR showed that the lesion had progressed, with vascular invasion (Fig. 1d-f).

Figure 1.

Case 1) Magnetic resonance imaging (MRI): T1 FatSat image shows hyperintensity of the tumor in segment VII secondary to necrosis with no arterial enhancement and no new lesions observed in the venous phase (a-c). The tumor seen on the previous MRI now shows activity and an increase in size (d-f). Case 2) Computed tomography (CT): 7 mm lesion with enhancement and a 17 mm lesion with typical behavior (g). Control image 2 months post-radiofrequency ablation shows the increase in size of the lesion from 7 mm to 25 mm, with a typical image of HCC (h).

Case 2

A 74-year-old woman was diagnosed with LC secondary to HCV in 2016. An ultrasound study performed before she started DAA therapy showed no focal lesions. After achieving SVR, she presented with acute cholecystitis. A tomography scan revealed 2 lesions, one measuring 7 mm that displayed typical HCC behavior, and the other measuring 1.7 cm that had contrast medium enhancement (Fig. 1g). A biopsy was performed on the larger lesion, and HCC was reported. The patient underwent radiofrequency ablation (RFA), and 2 months later, the lesion had increased in size from 7 mm to 2.5 cm (Fig. 1h).

Despite the fact that the development and recurrence of HCC observed in our case reports appear to be associated with DAA therapy, evidence from recent studies has shown no such association. In a cohort study on 33,137 patients, Mun et al. evaluated the risk of de novo HCC developing after antiviral treatment and concluded that there were no significant differences in HCC risk after DAA treatment.5 Those results were consistent for de novo cases and recurrence in a systematic review and meta-analysis by Rutledge et al. that included 138 studies (n = 177,512).6

The impact of DAA on liver transplantation has been evaluated in cohorts at European and Latin American centers, and in both of those studies, no evidence of higher waitlist progression or post-transplantation recurrence was reported.7,8 The controversy derived from previous analyses appears to be related to study methodology.

Today, the benefit of treating patients with DAAs is clear and has been associated with a decrease in all-cause mortality.9 Predictive scoring systems have been developed with the aim of stratifying the risk for HCC in patients that have undergone DAA therapy.10

Ethical considerations

The present scientific letter meets the current bioethical research regulations. It was authorized by the ethics committee of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”. The patients cannot be recognized or identified through the images or data contained in the article.

Financial disclosure

No financial support was received in relation to this article.

Conflict of interest

The authors declare that there is no conflict of interest.

A. Jemal, E.M. Ward, C.J. Johnson, et al.
Annual report of the nation on the status of Cancer, 1975–2014, featuring survival.
J Natl Cancer Inst, 109 (2017),
R. D’Ambrosio, C. Della Corte, M. Colombo.
Hepatocellular carcinoma in patients with a sustained response to anti-hepatitis C therapy.
Int J Mol Sci., 16 (2015), pp. 19698-19712
S. Grandhe, C.T. Frenette.
Occurrence and recurrence of hepatocellular carcinoma after successful direct-acting antiviral therapy for patients with chronic hepatitis C virus infection.
Gastroenterol Hepatol (N Y), 13 (2017), pp. 421-425
M. Reig, Z. Mariño, C. Perelló, et al.
Unexpected early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy.
J Hepatol, 65 (2016), pp. 719-726
E.J. Mun, P. Green, K. Berry, et al.
No difference between direct-acting antivirals for hepatitis C in hepatocellular carcinoma risk.
Eur J Gastroenterol Hepatol, 31 (2019), pp. 47-52
S.M. Rutledge, H. Zheng, D.K. Li.
No evidence for higher rates of hepatocellular carcinoma after direct-acting antiviral treatment: a meta-analysis.
Hepatoma Res, 5 (2019), pp. 31
L.S. Belli, G. Perricone, R. Adam, et al.
Impact of DAAs on liver transplantation: major effects on the evolution of indications and results. An ELITA study based on the ELTR registry.
J Hep., 69 (2018), pp. 810-817
F. Piñero, I. Boin, A. Chagas, et al.
Direct-Acting antivirals and hepatocellular carcinoma: no evidence of higher wait-list progression or posttransplant recurrence.
Liver Transpl., 26 (2020), pp. 640-650
F. Carrat, H. Fonatine, C. Dorival, et al.
Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study.
Lancet, 393 (2019), pp. 1453-1464
J. Tani, A. Morishita, T. Sakamoto, et al.
Simple scoring system for prediction of hepatocellular carcinoma occurrence after hepatitis C virus eradication by direct‐acting antiviral treatment: all Kagawa liver disease group study.
Oncol Lett, 19 (2019), pp. 2205-2212

Please cite this article as: Tapia-Sosa R, Hernández-Cabral F, Gabutti A, Páez-Zayas VM, García-Juárez I. Carcinoma hepatocelular asociado con el uso de la terapia antiviral de acción directa para virus de hepatitis C: reporte de dos casos. Revista de Gastroenterología de México. 2021;86:197–199.

Copyright © 2020. Asociación Mexicana de Gastroenterología
Revista de Gastroenterología de México
Article options
es en
Política de cookies Cookies policy
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here.