Screening

There is a very narrow therapeutic time frame for patients with HCC, as the prognosis is poor by the time patients have developed symptoms. Therefore, screening and surveillance are intended to identify HCC at the earliest possible stage, when treatment has the highest possible likelihood of cure.

One systematic review found that HCC surveillance is associated with improved tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis.[77] The addition of alpha-fetoprotein (AFP) testing to ultrasound screening significantly increases the sensitivity of early HCC detection in clinical practice.[78]

Guidelines on surveillance for HCC differ slightly in their recommendations. They all advise that patients with cirrhosis of any etiology should undergo screening, and most recommend that patients with hepatitis B without cirrhosis should also undergo screening if they have certain characteristics that put them at higher risk of HCC. The European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) specify that among patients with cirrhosis, only those with Child-Pugh class A or B disease should be screened. An exception is made for patients with Child-Pugh class C disease if they are awaiting liver transplant.[3]​​[79] [ Child Pugh classification for severity of liver disease Opens in new window ]

AASLD specifies that all patients listed for liver transplantation should undergo HCC screening twice a year because the priority for transplantation may change if a patient is detected with an early-stage HCC.[3]​ Surveillance is not recommended in patients with life-limiting comorbid conditions that cannot be cured by transplantation.[3]

All guidelines recommend that abdominal ultrasound is the screening modality of choice and should be performed every 6 months. AFP can be combined with ultrasound to enhance sensitivity, but it should not be used alone for surveillance because of its poor sensitivity and specificity.[3][52]​​​​​[63]​​​​[79][80]​​​ The UK National Institute for Health and Clinical Excellence specifies that AFP testing should be included for adults with cirrhosis and concomitant hepatitis B.[80]

Proteomic technology has led to the development of new molecular biomarkers, including des-gamma carboxyprothrombin (DCP), AFP-L3, and human growth factors. These may be used as potential screening tests and are being validated in clinical studies.[81]

Populations to screen

Patients with cirrhosis

Patients with cirrhosis of any etiology (including hepatitis B virus ([HBV], hepatitis C virus [HCV], alcohol, genetic hemochromatosis, metabolic dysfunction-associated steatotic liver disease, stage 4 primary biliary cirrhosis, and alpha-1-antitrypsin deficiency) should be enrolled for screening or surveillance.[3][52]​​​​​[63]​​​​[79][80]​​​​​

Patients with chronic HBV without cirrhosis

The National Comprehensive Cancer Network (NCCN) and EASL guidelines differ in their recommendations for the screening of patients with chronic HBV without cirrhosis:

  • NCCN guidelines recommend that all hepatitis B carriers without cirrhosis should be enrolled in an HCC screening program. They cite additional risk factors in this patient group as: platelet, age, and gender-HBV score ≥10; family history of HCC, man from endemic country ages >40 years, woman from endemic country ages >50 years, and person from Africa at earlier age.[63]​​

  • EASL guidelines advise that cost-benefit modeling is needed in this scenario. Experts recommend that surveillance is warranted if the HCC incidence is at least 0.2% per year. To help determine if patients meet this threshold, the PAGE-B (Platelet, Age, GEnder-hepatitis B) classification is used to stratify them into the following categories:[79][82]

    • low risk of HCC (PAGE-B score ≤9, almost 0% incidence of HCC at 5 years)

    • intermediate risk of HCC (PAGE-B score 10-17, 3% incidence of HCC at 5 years)

    • high risk of HCC (PAGE-B score ≥18, 17% incidence of HCC at 5 years).

    Screening is recommended for patients who fall into the intermediate and high-risk categories. The PAGE-B score is based on the decade of age (16-29 years = 0 points, 30-39 years = 2 points, 40-49 years = 4 points, 50-59 years = 6 points, 60-69 years = 8 points, ≥70 years = 10 points), sex (male = 6 points, female = 0 points), and platelet count (≥200 x 10⁹/L = 0 points, 100-199 x 10⁹/L = 1 point, <100 x 10⁹/L = 2 points). The PAGE-B score has yet to be validated in Asia. Individual risk assessment is recommended for patients in the low HCC risk class (PAGE-B score ≤9) who do not reach the 0.2%/year threshold for starting screening.[79]

Patients with HCV with bridging fibrosis

Additionally, some societies recommend screening noncirrhotic patients with HCV who have bridging fibrosis (stage F3, numerous septa without cirrhosis).[52][79] 

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