Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate

Table 1 Summary of studies of the association between direct-acting antiviral agents and de novo hepatocellular carcinoma occurrence

Ref.	Type of study	n (treated with DAAs)	Follow-up period	Incidence of HCC occurrence
Ravi et al[33]	Prospective	61	6 mo	9%
Conti et al[34]	Prospective	344	24 wk	3.16%
Cardoso et al[35]	Prospective	240	12 mo	7.4%
Mettke et al[38]	Prospective cohort treated with DAAs vs retrospective control matched group of untreated patients	158 in DAAs group vs 184 in the control group	440 d for DAAs group vs 592 d for the control group	2.9% vs 4.5%
Cheung et al[39]	Prospective cohort treated with DAAs vs retrospective control matched group of untreated patients	406 in each group	15 mo	4% in both groups
Calvaruso et al[40]	Prospective	2249	16 mo	3.5%
Romano et al[41]	Prospective	3917	536.2 + 197.6 d	1.4%
Kanwal et al[43]	Retrospective	22500	12 mo	1.18%
Finkelmeier et al[44]	Prospective	819	263 d	3.6% annually
Ioannou et al[45]	Retrospective	21948 treated with IFN free regimen	-	1.32% annually
Tani et al[46]	Retrospective	1088 (Patients with SVR)	4 yr	1.88% annually
Shiha et al[47]	Prospective	2372 patients with advanced liver fibrosis or cirrhosis with SVR	12 mo	2.3% annually
Pinero et al[48]	Prospective	1400	16 mo	2% annually
Lashen et al[49]	Retrospective	392 (F3-F4) patients	34 mo	7.6%
Hassany et al[50]	Prospective	350	2 yr after the end of treatment	6.7% in patients with SVR vs 23.8% in patients with non-SVR

DAAs: Direct-acting antiviral agents; HCC: Hepatocellular carcinoma; IFN: Interferon; SVR: Sustained viral response.

Table 2 Summary of Studies of the association between direct-acting antiviral agents and hepatocellular carcinoma recurrence

Ref.	Type of study	Number (treated with DAAs)	Median follow-up period	Incidence of HCC recurrence
Reig et al[56]	Retrospective	58	5.7 mo	27.6%
Conti et al[34]	Prospective	59	24 wk	28.81%
Calleja et al[58]	Retrospective	70	12 mo	30%
Elkassas et al[61]	Prospective	53 vs 63 untreated patients	16 mo vs 23 mo in the untreated group	37.7% vs 25.4%
ANRS study group[37]	Retrospective	(1) ANRS CO22 HEPATHER cohort: 189 vs 78 untreated patients	20.2 vs 26.2 mo	0.73 vs 0.66/100 person-mo
		(2) ANRS CO12 CirVir cohort: 13 patients received DAAs	79 mo	7.7%
Ogawa et al[64]	Prospective	152	1 yr	6.5% in non-cirrhotic and 23% in cirrhotic patients
Cabibbo et al[68]	Prospective	143	18 mo	29.1%
Huang et al[65]	Retrospective	62 receive DAAs vs 87 did not receive DAAs	12 mo	47% vs 49.8%
Singal et al[66]	Retrospective	304 received DAAs and 489 did not	365 d	17.1 vs 46.4%
Kinoshita et al[67]	Retrospective	147 received DAAs vs 156 received IFN	2 yr	60% vs 61%
Ikeda et al[71]	Prospective	89	2 yr	22.1%
Imai et al[72]	Retrospective	13 DAAs, 14 IFN, and 64 untreated groups	-	The 3-yr recurrence-free survival was 76.2% in DAAs group vs 69.2% in the IFN group and 22.4% in the untreated group
Gorgen et al[69]	Retrospective	875	-	the 5-yr recurrence-free survival was 93.4%, 84.8%, 73.9% for the pre-liver transplant DAA, IFN, and antiviral naïve groups
Tahata et al[70]	Retrospective	63 patients in each group	3 yr	43% in the DAAs vs 34% in the IFN group
Kamal et al[13]	Retrospective	52	2 yr	42.3%

DAAs: Direct-acting antiviral agents; HCC: Hepatocellular carcinoma; IFN: Interferon.