Non-Invasive Risk Stratification for Hepatocellular Carcinoma in HCV-Related Compensated Advanced Chronic Liver Disease Following Sustained Virological Response: Validation of the aMAP Score (HCV-aMAP)

Prediction of Risk of Hepatic Decompensation and Hepatocellular Carcinoma in Advanced Fibrotic or Cirrhotic Patients With Chronic Hepatitis C After Sustained Virologic Response

This retrospective cohort study evaluated the performance of non-invasive risk scores for predicting de novo hepatocellular carcinoma in adults with hepatitis C virus-related compensated advanced chronic liver disease who achieved sustained virological response after sofosbuvir-based direct-acting antiviral therapy. Patients treated at Siriraj Hospital between 2013 and 2023 were included if they had compensated advanced chronic liver disease and documented SVR12. The study compared FIB-4, APRI, ALBI, and aMAP scores calculated at SVR12 for prediction of hepatocellular carcinoma during long-term follow-up. The primary aim was to identify a very-low-risk subgroup in whom hepatocellular carcinoma surveillance might potentially be de-escalated.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection; Hepatocellular Carcinoma (HCC); Compensated Advanced Chronic Liver Disease
• Intervention / Treatment: Other: Non-invasive Risk Score Assessment

Detailed Description

This was a single-center retrospective cohort study conducted at Siriraj Hospital, Thailand. Consecutive adult patients with chronic hepatitis C virus infection and compensated advanced chronic liver disease who initiated interferon-free sofosbuvir-based direct-acting antiviral therapy between 2013 and 2023 and achieved sustained virological response at 12 weeks after treatment completion were included. Compensated advanced chronic liver disease was defined according to Baveno VII criteria, including histologic F3/F4 fibrosis, vibration-controlled transient elastography greater than 10 kPa, or clinical evidence of portal hypertension.

Baseline demographic, clinical, laboratory, and transient elastography data were collected from electronic medical records. The FIB-4, APRI, ALBI, and aMAP scores were calculated using laboratory values at SVR12. Patients with known or suspected hepatocellular carcinoma before direct-acting antiviral therapy, failure to achieve SVR12, or incomplete medical records precluding outcome assessment were excluded.

The primary outcome was de novo hepatocellular carcinoma during follow-up. Predictive performance of the non-invasive scores was assessed using time-to-event analysis, Kaplan-Meier methods, Cox proportional hazards regression, and time-dependent receiver operating characteristic curves at 1, 3, 5, and 8 years.

• Study Type: Observational
• Enrollment (Actual): 571

Contacts and Locations

Study Locations

• Thailand
  • Bangkok
    • Bangkok, Bangkok, Thailand, 10700
      • Siriraj Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with chronic hepatitis C virus infection and compensated advanced chronic liver disease who initiated sofosbuvir-based direct-acting antiviral therapy at Siriraj Hospital between 2013 and 2023 and achieved sustained virological response at 12 weeks after treatment completion.

Description

Inclusion Criteria:

• Age 18 years or older
• Chronic hepatitis C virus infection treated with direct-acting antiviral therapy
• Documented sustained virological response at 12 weeks after treatment completion
• Evidence of compensated advanced chronic liver disease before direct-acting antiviral therapy, defined by at least one of the following: histologic F3 or F4 fibrosis, vibration-controlled transient elastography >10 kPa, radiologic features compatible with advanced fibrosis or cirrhosis, or clinical or endoscopic evidence of portal hypertension
• Minimum follow-up of 12 months after sustained virological response

Exclusion Criteria:

• Incomplete or missing medical records precluding outcome assessment
• Known or suspected hepatocellular carcinoma before initiating direct-acting antiviral therapy
• Failure to achieve sustained virological response at 12 weeks

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HCV-related cACLD After SVR; Adults with hepatitis C virus-related compensated advanced chronic liver disease who achieved sustained virological response at 12 weeks after sofosbuvir-based direct-acting antiviral therapy and were followed for de novo hepatocellular carcinoma.	Other: Non-invasive Risk Score Assessment; FIB-4, APRI, ALBI, and aMAP scores were calculated using laboratory values at SVR12 to evaluate their performance for predicting de novo hepatocellular carcinoma during follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of de novo hepatocellular carcinoma	Occurrence of newly diagnosed hepatocellular carcinoma after achievement of sustained virological response (SVR12). Patients with known or suspected hepatocellular carcinoma before direct-acting antiviral therapy were excluded.	From SVR12 until diagnosis of hepatocellular carcinoma, last follow-up, or up to 8 years after SVR12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive accuracy of the FIB-4 score for de novo hepatocellular carcinoma	Time-dependent area under the receiver operating characteristic curve (AUC) of the FIB-4 score for predicting de novo hepatocellular carcinoma.	At 1, 3, 5, and 8 years after SVR12
Predictive accuracy of the APRI score for de novo hepatocellular carcinoma	Time-dependent area under the receiver operating characteristic curve (AUC) of the APRI score for predicting de novo hepatocellular carcinoma.	At 1, 3, 5, and 8 years after SVR12
Predictive accuracy of the ALBI score for de novo hepatocellular carcinoma	Time-dependent area under the receiver operating characteristic curve (AUC) of the ALBI score for predicting de novo hepatocellular carcinoma.	At 1, 3, 5, and 8 years after SVR12
Predictive accuracy of the aMAP score for de novo hepatocellular carcinoma	Time-dependent area under the receiver operating characteristic curve (AUC) of the aMAP score for predicting de novo hepatocellular carcinoma.	At 1, 3, 5, and 8 years after SVR12

Collaborators and Investigators

• Sponsor: Siriraj Hospital
• Investigators: Principal Investigator: Tawesak Tanwandee, MD, Siriraj Hospital

Publications and helpful links

General Publications

• Fan R, Papatheodoridis G, Sun J, Innes H, Toyoda H, Xie Q, Mo S, Sypsa V, Guha IN, Kumada T, Niu J, Dalekos G, Yasuda S, Barnes E, Lian J, Suri V, Idilman R, Barclay ST, Dou X, Berg T, Hayes PC, Flaherty JF, Zhou Y, Zhang Z, Buti M, Hutchinson SJ, Guo Y, Calleja JL, Lin L, Zhao L, Chen Y, Janssen HLA, Zhu C, Shi L, Tang X, Gaggar A, Wei L, Jia J, Irving WL, Johnson PJ, Lampertico P, Hou J. aMAP risk score predicts hepatocellular carcinoma development in patients with chronic hepatitis. J Hepatol. 2020 Dec;73(6):1368-1378. doi: 10.1016/j.jhep.2020.07.025. Epub 2020 Jul 21.
• de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76(4):959-974. doi: 10.1016/j.jhep.2021.12.022. Epub 2021 Dec 30.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Risk Stratification; Sustained Virological Response; HCC Surveillance; FIB-4; Direct-acting Antiviral Therapy; aMAP Score; APRI; ALBI Score
• Additional Relevant MeSH Terms: Blood-Borne Infections; Neoplasms by Site; Neoplasms; Infections; RNA Virus Infections; Virus Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Communicable Diseases; Carcinoma; Flaviviridae Infections; Hepatitis; Carcinoma, Hepatocellular; Hepatitis C
• Other Study ID Numbers: 984-2566-IRB1; Si 034/2024 (Other Identifier: Siriraj Institutional Review Board, Faculty of Medicine Siriraj Hospital, Mahidol University)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this study may be made available from the corresponding author upon reasonable request, subject to approval by the investigators and applicable institutional and ethical regulations.
• IPD Sharing Time Frame: Beginning after publication of the study results; no fixed end date.
• IPD Sharing Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal for purposes consistent with the approved study protocol and applicable ethical regulations. Requests should be directed to the corresponding author.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No