Independent Risk Factors for Hepatocellular Carcinoma Recurrence after Direct-Acting Antiviral Therapy in Patients with Chronic Hepatitis C

Abstract

Background/Aims This study was performed to evaluate the efficacy of direct-acting antivirals (DAAs) in Korean patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and to investigate the risk factors associated with HCC recurrence. Methods A total of 100 patients with HCV-related HCC, who were treated with DAAs between May 2015 and December 2016, were recruited from seven university hospitals in Korea. Claim data of 526 patients with HCC obtained from the Health Insurance Review and Assessment Service in South Korea were used for external validation of the results. Results Among the 100 patients, 88% achieved a sustained virological response (SVR) 12 weeks after the end of DAA therapy (SVR12), and 37% experienced HCC recurrence after DAA therapy. Short last HCC treatment durability (<12 months) before DAA commencement was independently associated with HCC recurrence (hazard ratio [HR], 2.89; p=0.011). In the nationwide validation cohort, 20.3% of the patients experienced HCC recurrence. The last HCC treatment with a noncurative method, a short last HCC treatment durability (<12 months), and a longer total duration of HCC treatment (≥18 months) were independently related with HCC recurrence (HR 3.73, p<0.001; HR 3.34, p<0.001; and HR 1.74, p=0.006; respectively). Conclusions DAA therapy showed an acceptable SVR12 rate in patients with HCV-related HCC. Short last HCC treatment durability (<12 months) was associated with HCC recurrence after DAA therapy. This finding suggests that the last HCC treatment durability is an important predictor of HCC recurrence after DAA therapy. (Gut Liver 2021;15-419)

Analyzing risk factors and developing a stratification system for hepatocellular carcinoma recurrence after interferon-free direct-acting antiviral therapy in chronic hepatitis C patients

“…In addition, several studies have reported that patients treated with DAAs <12 months following HCC treatment had higher HCC recurrence rates. 51,52 It is possible that studies showing high HCC recurrence rates in patients treated with DAAs shortly after HCC treatment may have been affected by selection bias, as they may have failed to detect small HCC nodules due to incomplete treatment before initiating DAAs. In the current study, the median time from the last HCC treatment with CRR to initiating DAA treatment was 7.8 months.…”

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

“…One of the most important predictors of HCC recurrence was history of HCC recurrence before DAA 8 , 13 , 32 together with the number of HCC treatments finally leading to CR achievement before anti-HCV therapies. 62 , 65 , 66 In addition, time elapsing between prior HCC treatment and DAA start was significantly associated with an increased risk of recurrent HCC in several studies, 38 , 64 , 67 , 68 where patients treated for HCC less than one year prior to DAA exhibited an increased risk of tumour recurrence. 38 , 68 Lastly, some authors reported that also prior HCC size, 13 number of nodules 38 and type of HCC treatment (ie, palliative vs curative) 38 , 67 were independently associated with HCC recurrence, although these data were not confirmed by others 8 , 22 , 65 ( Table 6 ).…”

“… 62 , 65 , 66 In addition, time elapsing between prior HCC treatment and DAA start was significantly associated with an increased risk of recurrent HCC in several studies, 38 , 64 , 67 , 68 where patients treated for HCC less than one year prior to DAA exhibited an increased risk of tumour recurrence. 38 , 68 Lastly, some authors reported that also prior HCC size, 13 number of nodules 38 and type of HCC treatment (ie, palliative vs curative) 38 , 67 were independently associated with HCC recurrence, although these data were not confirmed by others 8 , 22 , 65 ( Table 6 ). However, these results should be cautiously interpreted, as they are strongly influenced by study design and patients enrollment; recently, an individual patient-data meta-analysis pooling data of 977 patients from 21 studies have further enhanced the importance of pre-DAA HCC history and tumour burden.…”

Direct-Acting Antiviral Therapy and Risk of Hepatocellular Carcinoma Recurrence in Patients with Chronic Hepatitis C

“…In multivariate analysis, Ogawa et al 7 reported that the time between previous HCC treatment and DAA exposure within 1 year (hazard ratio, 3.20; 95% confidence interval, 1.29 to 9.65; p=0.0011) was significantly associated with HCC recurrence. In this issue of Gut and Liver, Ahn et al 1 also reported that a short last HCC treatment durability before DAA therapy (<12 months) was an independent risk factor of HCC recurrence in both a multicenter Korean cohort and a nationwide cohort from the Korean Health Insurance Review and Assessment Service database. The authors defined last HCC treatment durability as the time between the final HCC treatment and the start of DAA therapy.…”

“…SVR after DAA therapy may result in improved liver dysfunction in patients with hepatocellular carcinoma (HCC), but its impact on the risk of HCC recurrence has been the subject of controversy. In this issue of Gut and Liver, Ahn et al 1 reported that HCV-related HCC patients with complete response (CR) to treatment achieved acceptable SVR (88%) with DAA therapy, and 37% experienced HCC recurrence during the median follow-up period of 15.8 months (range, 4.4 to 29.9 months). Unfortunately, this study did not include a control group, which made it difficult to ascertain whether DAA therapy itself could increase or decrease the risk of HCC recurrence.…”