Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end

Table 3 Risk factors for de novo and recurrent hepatocellular carcinoma after direct-acting antiviral therapy

Ref.	Type of study	Patient (n) and characteristics	Risk factors
Conti et al[14]	Retrospective study	Cirrhotic patients treated with DAAs (n = 285)	No associated factor for de novo HCC, older age, liver stiffness for HCC recurrence
Singer et al[34]	Retrospective study	DAA-treated (n = 30183), IFN-treated (n = 12948), untreated (n = 137502)	Older age, male gender, cirrhosis, thrombocytopenia, portal hypertension, diabetes, tobacco use, alcoholic liver disease
Ioannou et al[35]	Retrospective study	DAA-treated (n = 21948), IFN-treated (n = 35871), DAA + IFN treated (n = 4535)	Non-SVR, cirrhosis
Kanwal et al[37]	Retrospective study	DAA-treated (n = 22500)	Non-SVR, alcohol use, non-African Americans, cirrhosis
Hanafy et al[71]	Prospectivestudy	All decompensated cirrhotic patients, DAA-treated (n = 160), untreated (n = 80)	An adequate baseline liver volume measured by ultrasound was associated with less HCC occurrence and better short-term survival
Kanwal et al[39]	Retrospective study	DAA-treated (n = 18076)	High FIB-4/APRI, alcohol use, older age, genotype 3
Watanabe et al[41]	Retrospective study	DAA-treated (n = 1438)	High FIB-4 index, AFP
Nagata et al[62]	Retrospective study	DAA-treated (n = 83), IFN-treated (n = 60)	IL-28 genetic polymorphism, post-treatment WFA+M2BP, AFP (> 5.4 ng/mL)
Ide et al[68]	Prospectivestudy	CHC DAA-treated (n = 2552)	Age ≥ 62 yr, male gender, FIB-4 index ≥ 4.6, GGTP level ≥ 44 IU/L
Calvaruso et al[69]	Prospective study	HCV cirrhosis DAA-treated (n = 2249)	Albumin < 3.5 g/dL, platelets < 120 × 109/L, absence of SVR
Romano et al[48]	Prospective study	CHC > F3 DAA-treated (n = 3917)	HBsAg+, APRI ≥ 2.5, CPT B, treatment failure
Sangiovanni et al[47]	Retrospective study	1161 HCC-free HCV cirrhotics, DAA treated, 124 HCV cirrhotics who had received a curative treatment for an HCC DAA treated	De novo HCC: Ascites, AFP, recurrent HCC: History of alcohol abuse, history of HCC recurrence

DAA: Direct-acting antivirals; FU: Follow-up; HCC: Hepatocellular carcinoma; SVR: Sustained virological response; IFN: Interferon; IQR: Interquartile range; LT: Liver transplant; CHC: Chronic hepatitis C; APRI: Aspartate aminotransferase to platelet ratio index; CPT: Child-Pugh-Turcotte; SVR: Sustained viral response; AFP: Alpha-fetoprotein; WFA⁺M2BP: Wisteria floribunda agglutinin positive Mac-2 binding protein; HCV: Chronic hepatitis C; GGTP: Gamma-glutamyl transpeptidase.