To assess the diagnostic accuracy of abdominal ultrasound and alpha-fetoprotein (AFP), alone or in combination, for the diagnosis of hepatocellular carcinoma (HCC) of any size and at any stage in people with chronic advanced liver disease, either in a surveillance programme or in a clinical setting.

• To assess the diagnostic accuracy of abdominal ultrasound and AFP, alone or in combination, for the diagnosis of resectable HCC in people with chronic advanced liver disease, either in a surveillance programme or in a clinical setting. The definition of resectable HCC is a neoplasm amenable to surgical radical resection according to the current guidelines (EASL-EORTC 2012; Omata 2017; EASL 2018; Heimbach 2018), that is, a single lesion with a maximum diameter of less than five cm, or fewer than three lesions with a maximum diameter of three cm.
• To compare the diagnostic accuracy of individual tests versus the combination of both tests.
• To investigate the following predefined sources of heterogeneity:
• study design (prospective compared to retrospective; case-control studies compared to cross-sectional cohort studies);
• study date (studies published before the year 2000 compared to studies published after the year 2000, due to advancements in technology and changes in diagnostic criteria);
• inclusion of participants without cirrhosis (studies including more than 10% participants without cirrhosis compared to studies including less than 10% participants without cirrhosis);
• study location (population differences): studies conducted in the Americas compared to Europe compared to Asia;
• prevalence of the target condition (studies with HCC prevalence more than 10% compared to studies with HCC prevalence less than 10%);
• participant selection (participants recruited from planned screening programmes compared to clinical cohorts);
• different HCC stage (studies with more than 20% of participants with resectable HCC compared to studies with less than 20% of participants with resectable HCC);
• different reference standard (histology of the explanted liver compared to liver biopsy compared to another reference standard);
• different liver cirrhosis aetiology (hepatitis C or hepatitis B virus associated cirrhosis compared to all other aetiologies);
• different severity of the underlying chronic liver disease (per cent of participants with MELD (model for end-stage liver disease) score less than 15 or Child Pugh score A);
• different AFP positivity cut-off values in studies using ultrasound and AFP in combination.