History

Fact Explanation
Right upper quadrant pain Most commonly due to the involvement of abdominal and pelvic visceral organs. [4] Some patients present with abdominal pain in the right upper quadrant secondary to spontaneous rupture of the hepatocellular carcinoma (HCC) and intra peritoneal bleeding. [3]
Weight loss Patients with HCC presents with a triad of right upper quadrant pain, weight loss and palpable mass. [4]
Symptoms of decompensated liver disease These include yellowish discoloration of the skin and mucus membranes, pruritus, edema of the lower limbs, abdominal distension and early satiety (due to worsening ascites). Some may present with variceal bleeding, either hematemesis or melena. [4]
Dyspnea Due to ascites. Malignant pleural effusions and pulmonary metastases may also contribute. [4]
Bone pain Due to bone metastasis. [6]
Risk factors for hepatocellular carcinoma (HCC) Cirrhosis is the main risk factor for the development of HCC. [2] Among the etiologies of cirrhosis chronic hepatitis B and C infection, alcoholic cirrhosis and non-alcoholic fatty liver disease plays a main role. Chronic hepatitis C has the highest risk. Less commonly, alpha-1-antitrypsin deficiency [7], autoimmune hepatitis,Wilson’s disease, sclerosing cholangitis and porphyrias play a role in the etiology of HCC. [1,2] In Asian and African countries aflatoxin also plays a role in etiology of HCC. [2] The risk of HCC in patients with cirrhosis varies depending on the etiology and the degree of liver damage. It ranges from 5% to 30%. [1]
References
  1. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 16 May 2014] Available from: doi:10.1056/NEJMra1001683
  2. MICHIELSEN PP, FRANCQUE SM, VAN DONGEN JL. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol [online] 2005 May 20:27 [viewed 16 May 2014] Available from: doi:10.1186/1477-7819-3-27
  3. CHEDID A, KLEIN P, TIBURI M, VILLWOCK M, BASSANI L, CHEDID M. Spontaneous rupture of hepatocellular carcinoma with haemoperitoneum: a rare condition in Western countries HPB (Oxford) [online] 2001, 3(3):227-230 [viewed 16 May 2014] Available from: doi:10.1080/136518201753242262
  4. SUN VC, SARNA L. Symptom Management in Hepatocellular Carcinoma Clin J Oncol Nurs [online] 2008 Oct, 12(5):759-766 [viewed 16 May 2014] Available from: doi:10.1188/08.CJON.759-766
  5. SHIH KL, CHEN YY, TENG TH, SOON MS. Long-term survival in a patient with repeated resections for lung metastasis after hepatectomy for ruptured hepatocellular carcinoma: a case report. J Med Case Rep [online] 2008 Jun 30:222 [viewed 16 May 2014] Available from: doi:10.1186/1752-1947-2-222
  6. KATYAL SANJEEV, OLIVER JAMES H., PETERSON MARK S., FERRIS JAMES V., CARR BRIAN S., BARON RICHARD L.. Extrahepatic Metastases of Hepatocellular Carcinoma1. Radiology [online] 2000 September, 216(3):698-703 [viewed 16 May 2014] Available from: doi:10.1148/radiology.216.3.r00se24698
  7. RUDNICK DA, PERLMUTTER DH. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology [online] 2005 Sep, 42(3):514-21 [viewed 16 May 2014] Available from: doi:10.1002/hep.20815

Examination

Fact Explanation
Fever Patients can be febrile. [3]
Signs of chronic liver disease [3] Patients are icteric with scratch marks, peripheral edema, spider nevie, palmar erythema, clubbing and gynecomastia.
Abdominal palpation The irregular, and nodular hepatomegaly is found in HCC. Often splenomegaly is detected. [3]
Hepatic bruit Usually a bruit is present over the HCC due to increased vasculature. [3]
Ascites According to the Child- Pugh score presence of ascites is a predictor of bad prognosis. [2,3]
Signs of hepatic encephalopathy Presence of hepatic encephalopathy is a bad prognostic sign. [2]
BMI Non-alcoholic fatty liver disease is associated with obesity. [1] Patients are cachectic with advanced disease.
References
  1. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 16 May 2014] Available from: doi:10.1056/NEJMra1001683
  2. LLOVET JM, REAL MI, MONTAñA X, PLANAS R, COLL S, APONTE J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet [online] 2002 May 18, 359(9319):1734-9 [viewed 16 May 2014] Available from: doi:10.1016/S0140-6736(02)08649-X
  3. SUN VC, SARNA L. Symptom Management in Hepatocellular Carcinoma Clin J Oncol Nurs [online] 2008 Oct, 12(5):759-766 [viewed 16 May 2014] Available from: doi:10.1188/08.CJON.759-766

Differential Diagnoses

Fact Explanation
Fibrolamellar Hepatic Cancer Commmonly seen in children and young adults of 20 to 40 years. This is not associated with cirrhosis and AFP is rarely elevated. This has a better prognosis than HCC. [1,2]
Cholangiocarcinoma Primary sclerosing cholangitis is a common risk factor for the development of both HCC and cholangiocarcinoma. [2]
Gallbladder carcinoma This has a high mortality and most tumors involve the liver at the time of diagnosis. [1]
Sarcoma of the liver Angiosarcoma, malignant mesenchymoma, teratosarcoma, and rhabdomyosarcoma primarily involve the liver. Commonly seen in childhood. [3]
Hepatoblastoma This is commonly seen in children less than three years of age. [2]
Hemangioma This is the commonest benign liver tumor. Usually patients are asymptomatic but hemangiomas can rupture and lead to fatal bleeding. [4]
Hepatic adenoma Another common benign neoplasm of the liver. Use of oral contraceptive pills is a known risk factor for the development of hepatic adenoma. [1]
Focal nodular hyperplasia This is believed to be estrogen sensitive and commonly seen in premenopausal females. [1]
Hepatic cyst Hepatic cysts are usually asymptomatic and detected incidentally. [5]
Metastatic liver cancer Metastatic deposits are commoner than primary liver tumors. Hematogenous metastasis arising from any tumor can metastasize in to the liver. However primary tumors in lung, breast, and colon are the commonest. [1]
References
  1. FIELDING L. Current Imaging Strategies of Primary and Secondary Neoplasms of the Liver Semin Intervent Radiol [online] 2006 Mar, 23(1):3-12 [viewed 16 May 2014] Available from: doi:10.1055/s-2006-939836
  2. EL-SERAG HB, DAVILA JA. Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study. Hepatology [online] 2004 Mar, 39(3):798-803 [viewed 16 May 2014] Available from: doi:10.1002/hep.20096
  3. CHIU O, FRANK JD, DOW CA. Hepatic angiosarcoma: detection with computed tomography. Australas Radiol [online] 2005 Apr, 49(2):163-5 [viewed 16 May 2014] Available from: doi:10.1111/j.1440-1673.2005.01366.x
  4. CHOI BY, NGUYEN MH. The diagnosis and management of benign hepatic tumors. J Clin Gastroenterol [online] 2005 May-Jun, 39(5):401-12 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/15815209
  5. KRAKORA GA, COAKLEY FV, WILLIAMS G, YEH BM, BREIMAN RS, QAYYUM A. Small hypoattenuating hepatic lesions at contrast-enhanced CT: prognostic importance in patients with breast cancer. Radiology [online] 2004 Dec, 233(3):667-73 [viewed 16 May 2014] Available from: doi:10.1148/radiol.2333031473

Investigations - for Diagnosis

Fact Explanation
Liver function tests Deranged liver function test reflects poor prognosis and survival. [5] However because of the large functional capacity of the liver, liver function tests may not show any derangement until late in the disease course. [6]
Serum alpha-fetoprotein (AFP) [1,13] AFP is elevated in about 75% of the patients with HCC. Levels more than 400 ng/mL predict the risk of HCC with specificity greater than 95%. [4] Rising levels more than 100ng/mL is often reflects the necessity of further investigations. [3] Serum AFP is useful in predicting survival as well. [5]
Ultrasound scan [1] Hepatic mass of 2cm or more is highly suggestive of HCC. Doppler scan is used to assess the perfusion of the tumor. [4]
Triple phase CTscan HCC typically shows early arterial enhancement and delayed washout in the venous phase in triple phase CT scan. This feature enables the differentiation of a HCC from hepatic metastasis focal nodular hyperplasia (FNH) and regenerating nodules. Vascular supply of the HCC originates from the hepatic artery (other above mentioned lesions are perfused by the portal vein) hence it shows early arterial enhancement. Multifocal lesions and portal vein thrombosis extending from the tumor mass all are highly suggestive of HCC. [1]
MRI Noncontrasted T1- and T2-weighted hepatic evaluation is used commonly. [4]
Biopsy of suspicious lesions This is not routinely done and only practiced if the definitive diagnosis cannot be made from imaging and biochemical studies. [7,13]
Investigations to diagnose a chronic viral hepatitis HBsAg, anti-HBc, anti-HCV assessment enable the diagnosis of chronic hepatitis B and C. [8,9,13]
Iron saturation Increased in hemochromatosis. [10]
Serum alpha-1-antitrypsin levels Reduced in alpha-1-antitrypsine deficiency. [11]
Serum calcium Ectopic parathyroid hormone production is an associated Para neoplastic syndrome in HCC. [12]
References
  1. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 16 May 2014] Available from: doi:10.1056/NEJMra1001683
  2. MICHIELSEN PP, FRANCQUE SM, VAN DONGEN JL. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol [online] 2005 May 20:27 [viewed 16 May 2014] Available from: doi:10.1186/1477-7819-3-27
  3. PENG SY, CHEN WJ, LAI PL, JENG YM, SHEU JC, HSU HC. High alpha-fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: significance of hepatitis virus infection, age, p53 and beta-catenin mutations. Int J Cancer [online] 2004 Oct 20, 112(1):44-50 [viewed 16 May 2014] Available from: doi:10.1002/ijc.20279
  4. FIELDING L. Current Imaging Strategies of Primary and Secondary Neoplasms of the Liver Semin Intervent Radiol [online] 2006 Mar, 23(1):3-12 [viewed 16 May 2014] Available from: doi:10.1055/s-2006-939836
  5. LLOVET JM, REAL MI, MONTAñA X, PLANAS R, COLL S, APONTE J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet [online] 2002 May 18, 359(9319):1734-9 [viewed 16 May 2014] Available from: doi:10.1016/S0140-6736(02)08649-X
  6. CAHILL BA, BRACCIA D. Current treatment for hepatocellular carcinoma. Clin J Oncol Nurs [online] 2004 Aug, 8(4):393-9 [viewed 16 May 2014] Available from: doi:10.1188/04.CJON.393-399
  7. SCHOLMERICH J. Diagnostic biopsy for hepatocellular carcinoma in cirrhosis: useful, necessary, dangerous, or academic sport?. Gut [online] 2004 September, 53(9):1224-1226 [viewed 16 May 2014] Available from: doi:10.1136/gut.2004.040816
  8. HESHAM M. ELGOUHARI, TAREK I. ABU-RAJAB TAMIMI, WILLIAM D. CAREY. Hepatitis B virus infection: Understanding its epidemiology, course, and diagnosis [online] Journal of Medicine December 2008 vol. 75 12 881-889. [viewed 16 May 2014] Available from: doi: 10.3949/ccjm.75a.07019
  9. LIA L. L. X.,GEORG M. L., JULIAN S. W., PAULO S. F. S., CLEBER F. G., et al. Prospective Follow-Up of Patients with Acute Hepatitis C Virus Infection in Brazil. Clin Infect Dis. [online] 2010: 50 (9):1222-1230. [viewed 10 April 2014] Available from: doi: 10.1086/651599
  10. ELLERVIK C, TYBJAERG-HANSEN A, NORDESTGAARD BG. Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis. J Intern Med [online] 2012 Jan, 271(1):51-63 [viewed 16 May 2014] Available from: doi:10.1111/j.1365-2796.2011.02404.x
  11. STOLLER JK, ABOUSSOUAN LS. Alpha1-antitrypsin deficiency. Lancet [online] 2005 Jun 25-Jul 1, 365(9478):2225-36 [viewed 16 May 2014] Available from: doi:10.1016/S0140-6736(05)66781-5
  12. GHOBRIAL MW, GEORGE J, MANNAM S, HENIEN SR. Severe hypercalcemia as an initial presenting manifestation of hepatocellular carcinoma. Can J Gastroenterol [online] 2002 Sep, 16(9):607-9 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12362213
  13. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166

Investigations - Fitness for Management

Fact Explanation
Full blood count Anemia can occur secondary to frequent variceal bleeding, poor nutrition and due to tumor deposits in the bone marrow. [5,6] A platelet count cab be low if splenomegaly is present secondary to portal hypertension. [6]
Serum electrolytes Hyponatremia is commonly seen in cirrhosis and ascites. Indicates poor prognosis. [4]
Serum creatinine [4] Elevated in hepato-renal syndrome. Preoperative assessment of baseline renal function is necessary.
Hepatic transaminases Elevated in active hepatocyte damage and in recent alcohol or hepatotoxic substance consumption. Baseline liver function should be optimum pre-operatively for a better outcome of surgical resection. [1] Hepatic transaminases may remain normal until late in the disease. [3]
Serum bilirubin Increased due to poor function and reduced number of hepatocytes. Patients with raised bilirubin have poor prognosis. [2] Bilirubin can be within the normal limits until significant amount of hepatocytes are damaged. [3]
Coagulation studies Prolonged PT/INR reflects diminished hepatic synthesis of coagulation factors. [7]
Serum albumin Serum albumin levels drop with derangement of liver function. Albumin level is used in calculation of prognostic information. (eg: Child-Pugh score) [2]
Random blood sugar Hypoglycemia is commonly seen in end stage liver disease due to diminished glycogen stores in the liver. [8]
References
  1. SUN VC, SARNA L. Symptom Management in Hepatocellular Carcinoma Clin J Oncol Nurs [online] 2008 Oct, 12(5):759-766 [viewed 16 May 2014] Available from: doi:10.1188/08.CJON.759-766
  2. LLOVET JM, REAL MI, MONTAñA X, PLANAS R, COLL S, APONTE J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet [online] 2002 May 18, 359(9319):1734-9 [viewed 16 May 2014] Available from: doi:10.1016/S0140-6736(02)08649-X
  3. CAHILL BA, BRACCIA D. Current treatment for hepatocellular carcinoma. Clin J Oncol Nurs [online] 2004 Aug, 8(4):393-9 [viewed 16 May 2014] Available from: doi:10.1188/04.CJON.393-399
  4. Practice advisory for preanesthesia evaluation. An updated report by the American Society of Anesthesiologists Task Force on Preanesthesia Evaluation. [viewed 16 May 2014]Available from: http://www.guideline.gov/content.aspx?id=36197
  5. OKADA T, KUBOTA K, KITA J, KATO M, SAWADA T. Hepatocellular carcinoma with chronic B-type hepatitis complicated by autoimmune hemolytic anemia: a case report. World J Gastroenterol [online] 2007 Aug 28, 13(32):4401-4 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17708620
  6. QAMAR AA, GRACE ND. Abnormal hematological indices in cirrhosis Can J Gastroenterol [online] 2009 Jun, 23(6):441-445 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721814
  7. SAJJADIEH M, VIUNYTSKA L. Prothrombin time in patients with and without fibrotic chronic liver disease. The Internet Journal of Pathology. [online] 2008: 8(1) [viewed 16 May 2014] Available from: http://ispub.com/IJPA/8/1/12789
  8. LANDAU BERNARD R., WILLS NOAH, CRAIG JAMES W., LEONARDS JACK R., MORIWAKI TAKESHI. The mechanism of hepatoma-induced hypoglycemia. Cancer [online] 1962 November, 15(6):1188-1196 [viewed 16 May 2014] Available from: doi:10.1002/1097-0142(196211/12)15:6<1188::AID-CNCR2820150616>3.0.CO;2-2

Investigations - Followup

Fact Explanation
Alpha feto-protein (AFP) Serum AFP levels should be assessed every 3 to 6 monthly in every patient who underwent surgical resection or liver transplantation. [1]
Ultrasound scan Postoperatively every patient should undergo liver imaging to detect the tumor recurrence. This should be done for atleast two years. [1]
References
  1. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166

Investigations - Screening/Staging

Fact Explanation
Serum alpha-fetoprotein [1,6] A biomarker and assessment should be done every 6 to 12 months. Raised AFP levels in a cirrhotic patient should raise the possibility of HCC.
Ultrasound scan [1] Done every 6-12 monthly. Suspected hepatic nodules should be followed up every 1 to 3 months. [6]
Chest X-ray Detects pulmonary metastasis. [6]
Contrast enhanced CT scan CT is considered as a good screening tool in some centers [3] but some argue it to be not cost effective [1] in HCC surveillance. But used in staging of the disease. Malignant deposits in the omentum, paracolic gutters, and subphrenic recesses, lungs and other organs can also be detected from CT scan. [1,2,5] A solitary mass without any evidence of vascular invasion is staged as T1. If there is evidence of vascular invasion it is T2. Multiple tumors of less than 5cm are also categorized in to T2. Multiple tumors of more than 5cm and single tumor which involves a major branch of the portal or hepatic veins is categorized as T3. Perforation of the visceral peritoneum and or extension to organs other than the gallbladder is considered T4. Metastasis in the regional lymph nodes (hilar, hepatoduodenal, or periportal) are detected in N1 stage. Presence of distant metastasis is M1. According to the TNM categorization HCC is categorized in to stages as stage 1 (T1 N0 M0), stage2 (T2 N0 M0), stage 3a (T33 N0 M0), stage 3b (T4 N0 M0), stage 3c (T1-4 N1 M0) and stage 4 (T1-4 N0-1 M1). [2] However TNM staging provides less prognostic information. [4]
MRI As for the CT scan MRI is also considered as a good screening tool [2] but some argue it to be not cost effective. [1] Non-contrasted T1- and T2-weighted hepatic evaluation MRI is considered to be the most sensitive investigation in HCC surveillance. [2] Both the primary tumor and the metastases can be evaluated with MRI. [5]
PET scan [5] PET scan is used for the diagnosis and evaluation of metastases of HCC.
References
  1. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 16 May 2014] Available from: doi:10.1056/NEJMra1001683
  2. FIELDING L. Current Imaging Strategies of Primary and Secondary Neoplasms of the Liver Semin Intervent Radiol [online] 2006 Mar, 23(1):3-12 [viewed 16 May 2014] Available from: doi:10.1055/s-2006-939836
  3. OLIVER JH 3RD, BARON RL, FEDERLE MP, ROCKETTE HE JR. Detecting hepatocellular carcinoma: value of unenhanced or arterial phase CT imaging or both used in conjunction with conventional portal venous phase contrast-enhanced CT imaging. AJR Am J Roentgenol [online] 1996 Jul, 167(1):71-7 [viewed 16 May 2014] Available from: doi:10.2214/ajr.167.1.8659425
  4. LLOVET JM, BRUIX J, FUSTER J, CASTELLS A, GARCIA-VALDECASAS JC, et al. Liver transplantation for small hepatocellular carcinoma: the tumor-node-metastasis classification does not have prognostic power. Hepatology [online] 1998 Jun, 27(6):1572-7 [viewed 16 May 2014] Available from: doi:10.1002/hep.510270616
  5. SHIH KL, CHEN YY, TENG TH, SOON MS. Long-term survival in a patient with repeated resections for lung metastasis after hepatectomy for ruptured hepatocellular carcinoma: a case report. J Med Case Rep [online] 2008 Jun 30:222 [viewed 16 May 2014] Available from: doi:10.1186/1752-1947-2-222
  6. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166

Management - General Measures

Fact Explanation
Health education Primordial prevention of HCC can be attempted by educating the public regarding the risk factors of cirrhosis. Educate the public regarding the possible ways of transmission of hepatitis B and C infection and the preventive measures. [3] Obese individuals should be encouraged to maintain normal BMI with healthy diet and regular exercise. People with harmful use of alcohol should be advised to quit alcohol consumption or at least to cut down it to safe limits. Diagnosed patients with cirrhosis should be encouraged to adhere to HCC screening surveillance and regular follow up. Patients with HCC should be well aware of possible treatment options available for them.
Psychological support Patients should be counseled regarding the disease prognosis and expected survival. Psychological support should be offered to each and every patient. Often patients have depression. Either psychotherapy or pharmacological treatment with antidepressants will be helpful. [4,5]
Hepatitis B vaccination Vaccination of at risk individuals (health care workers, babies born to hepatitis B infected mothers, commercial sex workers) will protect them from acquiring hepatitis B infection. [1,7]
Anti- hepatitis B immunoglobulin Neonates born to hepatitis B infected mothers benefit from early administration of anti- hepatitis B immunoglobulin. This prevent the infection hence the risk of HCC. [1]
Antiviral Treatment Patients with hepatitis B and C infection, if treated with antiviral drugs (interferon or lamivudine) have low risk of developing HCC. However antiviral treatment cannot abolish the risk of HCC. [1,2,7]
Analgesics Abdominal pain and bone pain can be managed with either non-steroidal anti-inflammatory drugs or opioids. Opioid analgesics should be reserved for moderate to severe pain. [4]
Treatment of anemia These include hematinic, erythropoietin or blood transfusion. [4,6]
Treatment of nausea and vomiting Antiemetics will be helpful to control nausea and vomiting. [4]
Treatment of constipation Oral laxatives can be prescribed. [4]
Treatment of malnutrition Patients often complain of poor appetite which results in malnutrition. Dietary counseling and nutritional supplementation (oral or parenteral) can be used to manage malnutrition. [4]
Management of ascites Some patients may benefit from diuretics but some require paracentesis. [4]
Management of jaundice Raised serum bilirubin causes pruritus. If jaundice is secondary to obstruction of the bile duct by the tumor, patients may require a biliary stent or percutaneous drainage. Cholestyramine and emollients will provide symptomatic control. [4]
Portal vein stenting Establish the patency of the portal vein. [7]
References
  1. EL-SERAG HASHEM B.. Hepatocellular Carcinoma. N Engl J Med [online] 2011 September, 365(12):1118-1127 [viewed 16 May 2014] Available from: doi:10.1056/NEJMra1001683
  2. SUNG J. J. Y., TSOI K. K. F., WONG V. W. S., LI K. C. T., CHAN H. L. Y.. Meta-analysis: treatment of hepatitis B infection reduces risk of hepatocellular carcinoma. [online] 2008 November, 28(9):1067-1077 [viewed 16 May 2014] Available from: doi:10.1111/j.1365-2036.2008.03816.x
  3. MICHIELSEN PP, FRANCQUE SM, VAN DONGEN JL. Viral hepatitis and hepatocellular carcinoma. World J Surg Oncol [online] 2005 May 20:27 [viewed 16 May 2014] Available from: doi:10.1186/1477-7819-3-27
  4. SUN VC, SARNA L. Symptom Management in Hepatocellular Carcinoma Clin J Oncol Nurs [online] 2008 Oct, 12(5):759-766 [viewed 16 May 2014] Available from: doi:10.1188/08.CJON.759-766
  5. ZABORA J, BRINTZENHOFESZOC K, CURBOW B, HOOKER C, PIANTADOSI S. The prevalence of psychological distress by cancer site. Psychooncology [online] 2001 Jan-Feb, 10(1):19-28 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11180574
  6. QAMAR AA, GRACE ND. Abnormal hematological indices in cirrhosis Can J Gastroenterol [online] 2009 Jun, 23(6):441-445 [viewed 16 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2721814
  7. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166

Management - Specific Treatments

Fact Explanation
Surgery Surgical resection of the tumor and liver transplantation are possible surgical options. Both are done with an intention to cure the disease. Surgical resection is a possible treatment option if the HCC is detected early (Stage 1, 2,3a and some 3b). [1] Surgical resection is considered as the gold standard in treatment. [2,5] Liver transplant is a treatment option done with curative intent. [1,3,5] TACE or RFA can be done as a neoadjuvant treatment to downstage the tumor. TACE, Y90 microsphere radioembolization or sorafenib can be given post operatively. Patients undergoing liver transplantation should be prescribed immunosuppressive therapy. [5]
Chemoembolization [2,5] Trans arterial chemoembolization (TACE) is one of the latest palliative treatment option for inoperable HCC. Chemoembolization is done using drug-eluting beads (DEB). [3,4]
Radiofrequency ablation (RFA) [2] This is also a palliative treatment option. Radiofrequency waves are focused with the aid of ultrasonography or CT guidance. Procedure can be done during laparoscopic and open surgical procedures as well. [5]
Other ablative procedures Percutaneous ethanol injection (PEI) [2], cryosurgery and microwave coagulation therapy are all used in ablation of the HCC. [5]
Yttrium-90 microsphere radio-embolization This is a mode of radiation therapy. It is targeted and delivered internally so a higher radiation dose can be used than in external radiotherapy. [5]
Chemotherapy Sorafenib, Cisplatin-based combinations, interferon-α, doxorubicin and infusional 5-FU are used. [5]
References
  1. FIELDING L. Current Imaging Strategies of Primary and Secondary Neoplasms of the Liver Semin Intervent Radiol [online] 2006 Mar, 23(1):3-12 [viewed 16 May 2014] Available from: doi:10.1055/s-2006-939836
  2. SUN VC, SARNA L. Symptom Management in Hepatocellular Carcinoma Clin J Oncol Nurs [online] 2008 Oct, 12(5):759-766 [viewed 16 May 2014] Available from: doi:10.1188/08.CJON.759-766
  3. DHANASEKARAN R, KOOBY DA, STALEY CA, KAUH JS, KHANNA V, KIM HS. Prognostic factors for survival in patients with unresectable hepatocellular carcinoma undergoing chemoembolization with doxorubicin drug-eluting beads: a preliminary study HPB (Oxford) [online] 2010 Apr, 12(3):174-180 [viewed 16 May 2014] Available from: doi:10.1111/j.1477-2574.2009.00138.x
  4. LLOVET JM, REAL MI, MONTAñA X, PLANAS R, COLL S, APONTE J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet [online] 2002 May 18, 359(9319):1734-9 [viewed 16 May 2014] Available from: doi:10.1016/S0140-6736(02)08649-X
  5. JELIC S., SOTIROPOULOS G. C.. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology [online] December, 21(Supplement 5):v59-v64 [viewed 16 May 2014] Available from: doi:10.1093/annonc/mdq166