| Study characteristics |
| Patient Sampling |
All consecutive HCC‐free Caucasian HBsAg‐positive mono‐infected patients with compensated cirrhosis starting tenofovir (TDF) or enticavir (ETV) between October 31, 2006 and April 1, 2014 at two tertiary Liver Centers in Milan, Italy, were evaluated for inclusion in this longitudinal cohort study, having a normal AFP levels at baseline, or within the first year of therapy.
28 patients were excluded from the study: 17 patients received TDF/ETV for less than one year, 3 developed HCC within the first year of treatment, 2 did not have regular monitoring of serum AFP, 3 had significant alcohol abuse (> 60 g/day for men and > 40 g/day for women assessed by patient's clinical interviews), and 5 who did not normalise AFP levels within the first year despite virological suppression.
Age range: 21‐83. Males 82% |
| Patient characteristics and setting |
|
| Index tests |
Serum AFP levels were determined by ImmunoAssay in Electrochemistry Luminescence ‘ECLIA’. Predefined cut‐off value 7 ng/mL |
| Target condition and reference standard(s) |
Contrast‐enhanced computed tomography (CT) or magnetic resonance imaging techniques were performed if liver ultrasound could not carefully evaluate the whole hepatic parenchyma during surveillance. As for internal protocol, whenever serum AFP increased > 7 ng/mL in patients with normal ALT levels and permanent undetectable HBV‐DNA, with no lesion detected by US, a CT scan or an MRI was performed within 3 months together with a new AFP determination. In patients with negative CT or MRI but still serum AFP levels persistently above the upper normal limit, a CT or MRI was repeated every 3 months. |
| Flow and timing |
The recurrence standard was performed within three months after the index test |
| Comparative |
|
| Notes |
Conflicts of interest: Massimo Iavarone: Speaking and Teaching: Bayer, Gilead Science, Janssen, BTG, Abbvie; Consultant for BTG. Mauro Viganò: Speaking and Teaching: Roche, Gilead Sciences, BMS. Mariagrazia Rumi: Speaking and Teaching: MSD, Abbvie, Gilead; Advisory board: Abbvie.
Angelo Sangiovanni: speaker bureau for Bayer, Gilead Science, Janssen, BTG, Abbvie, Novartis, Advisory board for Tiziana science. Massimo
Colombo: Grant and research support: BMS, Gilead Sciences; Advisory Committees: Merk, Roche, Novartis, Bayer, BMS, Gilead Sciences,
Tibotec, Vertex, Janssen Cilag, Achillion, Lundbeck, GSK, GenSpera, AbbVie, Alfa Wasserman; Speaking and teaching: Tibotec, Roche,
Novartis, Bayer, BMS, Gilead Sciences, Vertex, Merk, Janssen, Abbvie. Pietro Lampertico: Speaking bureau/advisory boards: BMS, Roche,
Gilead Sciences, GSK, MSD, Abbvie and Janssen, Eiger, Myr Pharma |
| Methodological quality |
| Item |
Authors' judgement |
Risk of bias |
Applicability concerns |
| DOMAIN 1: Patient Selection |
| Was a consecutive or random sample of patients enrolled? |
Yes |
|
|
| Was a case‐control design avoided? |
Yes |
|
|
| Did the study avoid inappropriate exclusions? |
No |
|
|
| Could the selection of patients have introduced bias? |
|
High risk |
|
| Are there concerns that the included patients and setting do not match the review question? |
|
|
High |
| DOMAIN 2: Index Test (AFP) |
| Were the index test results interpreted without knowledge of the results of the reference standard? |
Yes |
|
|
| If a threshold was used, was it pre‐specified? |
Yes |
|
|
| Could the conduct or interpretation of the index test have introduced bias? |
|
Low risk |
|
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? |
|
|
Low concern |
| DOMAIN 2: Index Test (US+AFP) |
| Were the index test results interpreted without knowledge of the results of the reference standard? |
|
|
|
| If a threshold was used, was it pre‐specified? |
|
|
|
| Could the conduct or interpretation of the index test have introduced bias? |
|
|
|
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? |
|
|
|
| DOMAIN 2: Index Test (US) |
| Were the index test results interpreted without knowledge of the results of the reference standard? |
|
|
|
| If a threshold was used, was it pre‐specified? |
|
|
|
| Could the conduct or interpretation of the index test have introduced bias? |
|
|
|
| Are there concerns that the index test, its conduct, or interpretation differ from the review question? |
|
|
|
| DOMAIN 3: Reference Standard |
| Is the reference standards likely to correctly classify the target condition? |
Yes |
|
|
| Were the reference standard results interpreted without knowledge of the results of the index tests? |
No |
|
|
| Could the reference standard, its conduct, or its interpretation have introduced bias? |
|
High risk |
|
| Are there concerns that the target condition as defined by the reference standard does not match the question? |
|
|
Low concern |
| DOMAIN 4: Flow and Timing |
| Was there an appropriate interval between index test and reference standard? |
Yes |
|
|
| Did all patients receive the same reference standard? |
No |
|
|
| Were all patients included in the analysis? |
Yes |
|
|
| Could the patient flow have introduced bias? |
|
High risk |
|
