الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide. It is the fifth most common cancer and the third cause of cancer-related death worldwide.
The incidence of HCC varies widely according to geographic location, with high incidence in sub-Saharan Africa and South East Asia.
Mostly, HCC arises in the setting of chronic liver disease, usually cirrhosis, HCC arising in a previously normal liver accounts for less than 10% of all HCCs.
The most frequent underlying cause of HCC is chronic hepatitis B, the next most common cause is hepatitis C. Other causes that predispose to HCC include alcoholic cirrhosis, NASH, aflatoxin BI and vinyl chloride exposure, hereditary hemochromatosis, α-1 antitrypsin deficiency, glycogen storage diseases and primary biliary cirrhosis.
Smoking, family history of HCC, and estrogen exposure are also implicated.
Most of the risk factors for HCC induce mutations in DNA and the genome, or facilitate the proliferation of hepatocytes and the fixation of DNA lesions. Different genetic alterations have been described in human HCC, including gain and loss of chromosomal DNA, allelic losses on several chromosomal regions, and mutations of oncogenes and tumor-suppressor genes.
HCC is frequently diagnosed late in its course because of the absence of pathognomonic symptoms and the liver’s large functional reserve. Symptomatic HCC has a very poor prognosis. The clinical presentation of HCC is variable from patient to patient. Late-stage disease usually presents as deterioration in clinical status in a patient known to have liver disease, or as new onset of right upper quadrant abdominal pain, weight loss, hepatomegaly, and ascites in patients not previously known to have liver disease.
Currently, there are multiple different staging systems for HCC. While each has strengths, none is ideal, as the characteristics of patients with HCC significantly impacts on the performance of various staging systems. The Barcelona Clinic Liver Cancer (BCLC) staging system is recommended by the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver, and seems well suited for use in most patients.
Strategies for prevention of HCC include Immunization against HBV, antiviral therapy for patients with HBV or HCV activity, screening of donated blood for the presence of hepatitis viruses, safe injection practices, altering agricultural practices to avoid contamination of foodstuffs by AFBI, and community-based programs to deal with excessive alcohol intake, smoking, obesity and diabetes.
Patients at risk for the development of HCC should undergo screening with ultrasonography at 6-month intervals. Abnormal ultrasound results should be investigated according to a special algorithm. Patients in whom HCC is not identified are nonetheless at risk and should be followed at 3-month intervals.
The commonly used tests for HCC diagnosis are assay for AFP and hepatic ultrasonography (US). Although widely used, AFP level has limited sensitivity and specificity for HCC, while US is dependent on the operator and limited in its ability to distinguish HCC from nonneoplastic lesions. Newer methods such as biomarkers or radiological assays are urgently needed.
Biomarkers are indicators of cellular, biochemical, molecular, or genetic alterations that distinguish normal and abnormal biological processes. The ideal biomarker for HCC would be sensitive and specific for HCC. The promising biomarkers for HCC include AFP-L3, Golgi protein 73, Glypican-3, α-L-fucosidase, PIVKA-II, Interleukin-8, hTERT mRNA, squamous cellular carcinoma antigen, Follistatin, Neighbor of Punc E11, and others.
Multidetector CT (MDCT) and MRI are the likely next step (following US) in imaging of suspicious liver nodules. Lipiodol CT has a complementary role to MDCT. The use of contrast-enhanced US and superparamagnetic iron oxide-enhanced MRI is likely to improve the sensitivity for HCC detection. Positron emission tomography (PET) using FDG is now well established as a noninvasive diagnostic tool for HCC. FDG- PET/CT has a sensitivity of HCC detection to close to 100%.
Liver resection is the treatment of choice for HCC in non-cirrhotic patients. Currently, liver transplantation stands as the best treatment modality for early-stage HCC in patients with decompensated cirrhosis, giving patients the opportunity to be free from the potentially lethal complications of both cancer and their underlying liver disease, thus, expansion of the HCC criteria for liver transplantation must be justified. A successful living donor liver transplantation programs in Egypt is now existing.
Percutaneous ablation is the best treatment option for patients with early stage HCC who are not suitable for resection or transplantation. Currently, RFA should be the first choice for local ablation, but PEI remains an important therapeutic tool.
Regional therapy causes tumor necrosis and tumor control while preserving as much functional liver tissue as possible, regional therapies include TAE, TACE, and TARE. TAE and TACE are considered for patients with nonsurgical HCC that are also ineligible for percutaneous ablation, provided there is no extrahepatic tumor spread.
Sorafenib is a multikinase inhibitor with reported activity against cellular differentiation receptors, and is recommended as first line option in patients who can not benefit from resection, transplantation, ablation or TACE, and still have preserved liver function.