Risk of de novo Hepatocellular Carcinoma after HCV Treatment with Direct-Acting Antivirals

Abstract

Background and Aims: The aim of the study was to evaluate the risk of hepatocellular carcinoma (HCC) development after treatment with direct-acting antivirals (DAAs) and to compare HCC occurrence in these patients with that among patients treated with interferon (IFN)-based therapies. Methods: We analyzed a large cohort with chronic hepatitis C virus patients for the onset of new HCC after DAA treatment. A historical IFN-treated cohort was investigated for comparison. Results: A total of 819 patients were included in the DAA group. The median follow-up period was 263 days (0–1,001). Twenty-five patients (3.6 HCCs/100 person-years; 3.1%) were diagnosed with de novo HCC within the time of observation. No patient without cirrhosis had developed HCC. Patients with newly diagnosed HCC were mostly male, older, and treatment-experienced and had a lower 12-week sustained virologic response (SVR12) rate and higher levels of liver inflammation markers. The median time to HCC was 312 days (0–880). Investigation of the subcohort of 269 cirrhotic patients yielded an HCC rate of 8.9 HCCs/100 person-years. In this cohort, non-SVR12 was an independent risk factor for de novo HCC (HR 4.48; 95% CI 1.51–13.12; p = 0.007). Twenty-four patients (96%) with new HCC were Child-Pugh class A and 17 (68%) were diagnosed in early BCLC stage A. For the IFN-treated patients, we calculated an overall risk of HCC occurrence of 1.3/100 person-years (19 patients out of 351; 5.4%). The median time to diagnosis was 38.8 months (0–113). Conclusion: The de novo HCC rates did not differ between the DAA-treated patients and those who received IFN. Achievement of SVR is of utmost importance for HCC prevention.

Serum sphingolipids predict de novo hepatocellular carcinoma in hepatitis C cirrhotic patients with sustained virologic response

“…This immunologic hypothesis may be of further interest regarding the ongoing debate whether treatment of HCV infection with DAAs could potentially even increase the risk of HCC occurrence and recurrence compared to interferon (IFN)‐based treatments . However, as we have recently shown, there is a growing body of evidence that HCC occurrence and recurrence rates do not increase but even decrease following DAA therapy and are comparable to those reported in the IFN era . Nahon et al recently pointed out, that age, diabetes and reduced liver functions, as well as different screening intensity can explain the apparent increase of HCC incidence in patients after DAA‐therapy compared to patients who received IFN therapy .…”

“…39,40 However, as we have recently shown, there is a growing body of evidence that HCC occurrence and recurrence rates do not increase but even decrease following DAA therapy and are comparable to those reported in the IFN era. 41 Despite of our promising new data, our current study had some limitations. We analysed SL concentrations in a retrospective setting and therefore we cannot prove underlying mechanistical relationships.…”

Effect of Successful Direct Acting Antivirals Therapy on Liver Stiffness in Patients with Chronic HCV Infection

“…Fibrosis becomes more harmful and progresses to liver cirrhosis [16] . Most HCV-associated hepatocellular carcinoma is seen with experience of liver fibrosis or cirrhosis [17] . Recent options of HCV treatment as DAAs can efficiently eradicate the virus, but regression of hepatic fibrosis in all patients is not the same.…”

Review on chemogenomic approaches towards hepatitis C viral targets

“…SVR rates varies for particular genotypes, that is, genotype 1 shows around 42‐58%, genotype 2 shows 80%, genotype 3 and 4 shows 66% or 63‐69%, respectively . However, some studies have reported that recurrence of HCC in chronic hepatic patients even after they achieve SVR in DAA treatment …”