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DNA has been shown to be a predictor of HCC development Unfortunately ultrasound is highly operator dependent with
synergistic with inflammation. Viral DNA replication and a variable sensitivity of 30-70%, and most importantly < 20%
[17]
hepatitis B core antigen expression are halted in HBV HCC, while of patients compliant with biannual exams. [36-38]
20% of cells persist production of hepatitis B surface antigen
triggering an immune responses and the secretion of cytokines DIAGNOSIS
tumor necrosis factor-, interferon and interleukin-2, which can
down regulate the accumulation of HBV RNAs. [18-20] Hepatocellular carcinoma is diagnosed by contrast-enhanced
computerized tomography (CT) or magnetic resonance
Development of HCV-related HCC is a multistep process imaging (MRI). Early arterial phase enhancement is seen
including the up regulation of inflammatory cytokines and in the tumor followed by venous phase dropout. These
induction of oxidative stress from chronic hepatitis, fibrosis, characteristics carry result in 90% sensitivity and 95%
liver regeneration, and cirrhosis. The intermediate step specificity for lesions greater than one centimeter. In
[39]
[21]
is represented by dysplastic nodules with the coexistence 2013, the American College of Radiology introduced the
of epigenetic and genetic changes that develop into HCC. Liver Imaging Reporting and Data System to standardize the
Multiple pro-inflammatory states appear to be synergistic reporting and data collection of CT and MRI for HCC. In
[40]
with HCV including: alcohol, HBV and HIV co-infection, efforts to improve lower cost technology, contrast-enhanced
diabetes mellitus, older age, African American race, ultrasound was introduced with a 90% sensitivity, 99%
thrombocytopenia, and smoking. [21-24] specificity and 89% diagnostic accuracy. The diagnostic
[41]
accuracy of MRI has been improved by dual contrast
Nonalcoholic fibrotic liver disease and NASH is an entity agents like Eovist , which is a hepatobiliary excretion
®
[42]
previously classified with cryptogenic cirrhosis with a high and vascularization markers used to diagnosis HCC.
relative risk for HCC. Pro-inflammatory states from fatty Despite these advances in technology, diagnostics are
acids release cytokines, pro-oncogenic signals and stimulate still encumbered by operator variability and inadequate
[18]
epigenetic changes even in the absence of cirrhosis. diagnostic resolution in tumors under 2 cm. The deficiencies
Subsequently obese type II diabetics are at twice the risk in diagnostic screening and sensitivity are seen by the mean
to develop HCC. [25-27] Alternatively, African Americans are at tumor size of HCC with the state of Louisiana being 6.5 cm
a lower relative risk for HCC compared to Caucasians based well above Milan Criteria.
on fat distribution and metabolism. The estimated yearly
incidence of HCC development in NASH-cirrhosis (2.6%) is STAGING AND PROGNOSIS
similar to HCV-cirrhosis (4%). [28]
Multiple staging systems exist for HCC, but the Barcelona
Genes involved in hepatocarcinogenesis include p53, PIKCA, Clinic Liver Cancer (BCLC) staging, and prognostic system
and ß-catenin. In addition, there are two signaling pathways appear to be the most widely accepted. BCLC incorporates
for cellular differentiation that are frequently disrupted: tumor stage, cirrhosis stage, and functional performance
(1) Wnt-ß-catenin and (2) Hedgehog. WNT signaling appears status and links stage with a treatment algorithm. [43-45]
to be associated with a higher incidence of transformation Despite multiple valid staging systems, the most attractive
and pre-neoplastic adenomas. [29] system would be the staging of HCC on genomic finger
printing directing therapy and resource allocation such as
SURVEILLANCE liver transplants.

The American Association for the Study of Liver Diseases Very early stage HCC (Stage 0) are tumors < 2 cm have the
advocates bi-annual ultrasound surveillance for high-risk best prognosis but are hard to identify on imaging. Early stage
patients. Cost-effectiveness is meet with two criteria: HCC (Stage A) is solitary lesions or up to three lesions < 3 cm
[30]
(1) annual incidence > 1.5% per year and (2) threshold with preserved liver function (Child-Pugh Class A or B) and
of $50,000 per quality-adjusted life year (QALY). Several reasonable functional status (PS 0-2) with. Their 5-year
economic analyzes confirm Child-Pugh Class A patients survivals reach 50-75%. Intermediate stage HCC (Stage B)
increase life expectancy with cost effectiveness of $26,000 and is multi-nodular with preserved liver function (Child-Pugh
$55,000 per QALY. The best data on surveillance comes from a Class A or B) and good functional status (PS 0), and no
prospective Chinese trial. [31-35] Surveillance is recommended for cancer-related symptoms or evidence of vascular invasion.
all cirrhotics, HBV carriers if they are Africans older than age Advanced stage HCC (Stage C) demonstrates vascular invasion
20 years, Asians older than 40 years or have a family history or extra-hepatic spread with compromise of functional
of HCC. However, debate on the utility of AFP continues. status (PS 1 or 2) due to HCC. Terminal stage HCC (Stage D)

2 Hepatoma Research | Volume 1 | Issue 1 | April 15, 2015