Hepatocellular carcinoma after direct‐acting antiviral drug treatment in patients with hepatitis C virus

Abstract

Background and Aim Given the use of direct‐acting antivirals (DAAs) to treat hepatitis C virus (HCV), their effects on hepatocarcinogenesis should be determined. Methods This study enrolled 349 patients with HCV who underwent DAA treatment at our hospital between 2014 and 2018. Their median age was 65 years, and 184 were male; 301 cases were of HCV serotype 1, and 48 were of serotype 2. The DAA treatment was daclatasvir/asunaprevir in 107 cases, sofosbuvir (SOF)/ledipasvir in 147 cases, ritonavir‐boosted ombitasvir/paritaprevir in 28 cases, elbasvir/grazoprevir in 19 cases, and SOF/ribavirin in 48 cases. The patients’ histories included hepatocellular carcinoma (HCC) in 45 cases, liver transplant (LT) in 10 cases, and kidney transplant (KT) in 17 cases. Results Sustained virological responses occurred in 335 cases (96%). DAA treatment was initiated a median of 16.3 months after HCC treatment. After DAA treatment, 15 cases (33%) had recurrence of HCC after a median of 11.6 months, and 3 cases (1%) developed de novo HCC. Six LT patients and one KT patient had HCC; however, no HCC was observed after DAA. The incidence of HCC was significantly higher in patients with multiple HCC treatments in the Cox hazard model (hazard ratio 1.664, 95% confidence interval 1.134–2.441, P < 0.01). Surgical resection or LT reduced the risk of HCC. Conclusions DAA did not increase the rate of HCC, even in immunosuppressed patients. However, careful follow‐up for HCC recurrence is required in previously treated cases.

Liver Remodeling on CT Examination in Patients with HCV Compensated Cirrhosis Who Achieved Sustained Virological Response after Direct-Acting Antivirals Treatment

“…Direct acting antivirals (DAAs) introduced in 2014 have represented a revolution for the treatment of patients with HCV due to high sustained virologic response (SVR) rate (95-100% in genotype 1) and excellent tolerability [3,4]. Despite the proven SVR, there is still a risk of developing HCC that justifies careful monitoring of these patients [5].…”

<p>Timing of DAA Initiation After Curative Treatment and Its Relationship with the Recurrence of HCV-Related HCC</p>

“…No significant difference was found in the starting time of DAA between the HCC recurrent and nonrecurrent groups. 29 This result was supported by Degasperi et al, although HCC recurred in 7/17 (41%) patients starting DAA≤6 months from previous HCC treatment versus 13/43 (30%) patients starting DAA treatment >6 months (P=0.54), time interval between HCC treatment and DAA start could not predict HCC recurrence at univariate analysis. 30 As suggested by several studies, the early recurrence of HCC may not be related to whether to use DAA but likely to the time of DAA initiation.…”

“…Kogiso et al confirmed that DAA did not increase the rate of HCC, even in patients who received immunosuppressive therapy in a retrospective study. 29 may reduce the second recurrence following curative treatment after the first recurrence in a landmark time analysis. 46 This finding aligned with previous results reporting that interferon treatment can reduce the second relapse but not the first relapse.…”

Elevation of Memory Cytotoxic T Lymphocytes, Including Human T Lymphotropic Virus Type 1 Tax-Specific and Hepatitis Virus Type C-Specific Cytotoxic T Lymphocytes, in a Patient with Adult T-Cell Leukemia/Lymphoma and Hepatocellular Carcinoma

“…The cause of HCC development after obtaining sustained virological response with DAA treatment is currently unknown [5]. One possible cause of HCC pathogenesis is an immunological mechanism [6]. Sustained HCV infection causes chronic inflammation in liver cells by triggering an immune response.…”