Hepatocellular carcinoma risk after viral response in hepatitis C virus-advanced fibrosis: Who to screen and for how long?

Table 1 Studies assessing the risk of hepatocellular carcinoma according to baseline and dynamic risk factors

Ref.	Country	n	Population at risk	Diagnosis of cirrhosis	Treatment regimens	Baseline risk factors	Dynamic risk factors
Lleo et al[33], 2019	Italy	1766	All cirrhosis 11.4% Child B/C	1 or more of the following: Stage 4 fibrosis by METAVIR score, esophageal and/or gastric varices at endoscopy, LSM > 12.5 kPa	All were treated with DAA	Age > 50 years old and presence of esophageal varices, platelets < 110000/L and LSM > 25 kPa	Lack of SVR
Ioannou et al[44], 2018	United States	45810	23% cirrhosis	Clinical, based on ICD-9 or 10 codes for cirrhosis or its complications	Either IFN or DAA	Cirrhosis, SVR, ALT, AST, platelets, albumin, age
Ioannou et al[45], 2019	United States	48135	9784 with pretreatment cirrhosis	Clinical, based on ICD-9 or 10 codes for cirrhosis or its complications	Either IFN or DAA	Cirrhosis and FIB-4 ≥ 3.25 before treatment	FIB-4 ≥ 3.25 post-SVR
Ravaioli et al[47], 2018	Italy	139	All cirrhosis; Included previous HCC 11.5% Child B		All were treated with DAA	History of previous HCC	Child B and LSM reduction after DAA treatment < 30%
Pons et al[48], 2019	Spain	572	All LSM ≥ 10 kPa; All compensated	cACLD defined by LSM ≥ 10 kPa	All were treated with DAA	High risk: baseline albumin < 4 g/dL; Low risk: Baseline albumin ≥ 4 g/dL	High risk: LSM ≥ 20 kPa or LSM 10-20 kPa and albumin < 4.4 g/dL; Low risk: LSM < 10 kPa or LSM 10-20 kPa and albumin ≥ 4.4 g/dL
Fan et al[50], 2020	China	3566	75.3% cirrhosis compensated and decompensated	Histological and/or radiological	Either IFN or DAA	aMAP score; Low risk: 0-50; Intermediate risk: 50-60; High risk: 60-100
Alonso et al[49], 2020	Spain	993	Advanced fibrosis or compensated cirrhosis	Clinical or histological; advanced fibrosis defined by a LSM by TE > 9.5 Kpa	All were treated with DAA	Albumin < 4.2 g/dL; LSM > 17,3 kPaFIB-4 > 3.7	Delta LSM < 25.5%; FIB-4 > 3.3; GGT > 42 IU
Ioannou et al[62], 2020	United States	48151	All cirrhosis compensated and decompensated	Clinical, based on ICD-9 or 10 codes for cirrhosis or its complications	Either IFN or DAA	Deep learning RNN model
						Cirrhosis diagnosis, sex, race and HCV genotype 3	Development of cirrhosis, SVR, BMI, AST, ALT, bilirubin, FIB-4, APRI, platelets

LSM: Liver stiffness measurement; TE: Transient elastography; INF: Interferon, DAA: Direct-acting antiviral agent; HCV: Hepatitis C virus; SVR: Sustained virologic response; FIB-4: Fibrosis 4; HCC: Hepatocellular carcinoma; c-ACLD: Compensated advanced chronic liver disease; CP: Child-Pugh; FU: Follow-up; amap: age, male, ALBI and platelets; GGT: Gamma-glutamyltransferase; RNN: Recurrent neural networks; APRI: AST to platelet ratio index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index.