Patients with HCC usually present in advanced stages of the disease because of the absence of pathognomonic symptoms [5, 6]. The median survival following diagnosis is approximately 6–20 months [7].

Patients are largely asymptomatic, apart from symptoms of existing chronic liver disease. A diagnosis of HCC should be suspected in situations of recent onset hepatic decompensation in a patient with compensated chronic liver disease. Table 1.2 lists the common presenting symptoms and signs. Tumor rupture with intraperitoneal bleed is a rare clinical presentation which requires urgent resuscitation, angioembolization, or even surgery.

HCC can occasionally be associated with paraneoplastic syndromes like hypoglycemia, erythrocytosis, hypercalcemia, or severe watery diarrhea.

Triple-phase contrast-enhanced CT scan or MRI is the investigative modality of choice for HCC. A diagnosis of HCC can be made for a solid liver lesion with characteristic enhancement patterns, i.e., enhancement in the arterial phase and contrast washout in the venous phase. Both arterial enhancement and venous washout are essential to make a diagnosis of HCC.

As the majority of patients with HCC have pre-existing chronic liver disease, enrolling these patients into a surveillance program of 6-monthly ultrasound aids in early diagnosis. Fig. 1.1 shows the American Association for the Study of Liver Diseases (AASLD) algorithm for suspected HCC [8]. Differentiation between high-grade dysplastic nodules and HCC on biopsy may be challenging and requires evaluation by expert pathologists supplemented with staining for glypican 3, heat shock protein 70, and glutamine synthetase. If the biopsy is negative for HCC, patients should be followed by imaging at 3- to 6-month intervals until the nodule either disappears, enlarges, or displays diagnostic characteristics of HCC.

Serum alpha-fetoprotein (AFP) levels are not included in the diagnostic algorithm for HCC as elevated serum AFP may also be seen in patients with chronic liver disease without HCC such as acute or chronic viral hepatitis [9]. However, it is accepted that serum AFP levels greater than 500 μg/L, in a high-risk patient, are diagnostic of HCC [10]. Serum AFP has also emerged as an important prognostic marker in patients being evaluated for liver transplant. An AFP level >1000 μg/L is associated with a high risk for disease recurrence following transplant [11].

The most common sites of extrahepatic metastases in HCC are the lungs, abdominal lymph nodes, and bones, in that order. A CT chest is recommended for all patients being considered for curative resection. On account of low diagnostic yield a bone scan is only recommended for symptomatic patients.

Table 1.3 shows the TNM staging for HCC [12].