Symptoms
Hepatocellular carcinoma inicially is asymptomatic during initial phase. Symptoms of advanced disease are abdominal pain (right upper quadrant) and weight loss in patients with cirrhosis. This shift toward earlier diagnosis is largely attributed to surveillance programs for patients with chronic liver disease. Because HCC often coexists with cirrhosis, its onset is frequently marked by a sudden, unexplained deterioration in the patient’s condition.
Physical findings depend on the stage of the disease. In the early stages, patients may show signs of cirrhosis, or findings may be entirely absent. In advanced disease, the liver is almost always enlarged, often significantly, and hepatic tenderness is common, particularly in later stages. The surface of the liver may feel smooth, irregular, or nodular. An arterial bruit, rough in character and heard during systole, may be audible over the tumor and remains unaffected by changes in the patient’s position.
Abdominal Ultrasound
US remains the mainstay test for diagnosis of HCC. Surveillance is associated with improved early detection, curative treatment, and improved survival.
Any expected yearly incidence of >1% in cirrhosis or >0.2% in non cirrhotic is deemed cost-effective. This includes all etiology cirrhosis, in which the recommendation is screening with US every 6 months. In certain groups of non cirrhotic Hepatitis B chronic infections 6 monhtly surveillance is also recommended based on the PAGE-B score ≥ 10 or the Reach Score . Other groups as haemochromatosis with F3 (advanced fibrosis) are suggested to be screened every 6 months.
Non-cirrhotic chronic B hepatitis 6 months surveillance:
- Man from endemic country age >40 y
- Woman from endemic country
age > 50 y - Person from Africa at earlier age
- Family history of HCC
- PAGE-B score ≥ 10
Note that surveillance is not recommended in patients who are not fit for cancer-specific therapy. In instance, decompensated cirrhosis (Child-Pugh-Turcotte >B9 who would not be candidates for surgery or liver transplant if HCC was diagnosed, and those with very impaired performance status (Eastern Cooperative Oncology Group (ECOG > 2)
AFP (Alpha fetoprotein)
AFP is an albumin-like glycoprotein which performs similar functions to albumin in fetal circulation. It is initially produced by the yolk sac, but by 13 weeks of gestation the foetal liver is the main source. After birth, levels in the infant decline rapidly during the first year and reach a low basal range by the end of the second year. These low levels of between 0 and 10 IU/mL are maintained throughout normal adult life.
Combination of AFP (cut-off point of 20 ng/mL) and ultrasound: for any stage HCC they have a sensitivity 96% and specificity 85%. Note that US alone has a sensitivity 72% and specificity 94%. Some loss of specificity can happen when adding AFP as high AFP can also be seen in non HCC individuals, such as hepatitis , cirrhosis, cigarette smoking or germ cell tumors. Level >200 ng/ml strongly suggest HCC with a specificity of 99%. The AASLD and BSG guidelines suggest 6 monthly US+ AFP, whereas the EASL suggest US with or without AFP.
Other modalities
More biomarkers are becoming available and their performance looks promising.
Alpha fetoprotein L3 (AFP-L3) and Des-carboxy-prothrombin (DCP) among others. The combination with other transaminases as well as demographic such as age or gender are the base for scores such as GALAD or Doylestown plus which could have a Sensisitivity and Especificity of 90% and 95%, opening the door to future screening with only blood tests.