Hepatocellular Carcinoma

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Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Laboratory 8 Radiology 9 Staging 10 Complications 11 Differential-diagnosis 12 Management 13 More General Terms 14 Additional Terms 15 Internet Database 16 References

More Specific Terms

• hepatocellular carcinoma [TP53/ARG249SER]
• hepatocellular carcinoma [TP53/VAL157PHE]

Etiology

• risk factors

• hepatitis B virus
• hepatitis C virus
• aflatoxin
• anabolic steroids
• hepatic cirrhosis

• 30% lifetime risk with cirrhosis & hemochromatosis
• uncommon with primary biliary cirrhosis
• uncommon with hepatolenticular degeneration ( Wilson's disease)
• diabetes further increases risk
• obesity further increases risk

Epidemiology

• more common in Asia & Africa than in North America & Europe

Pathology

• often dysplastic hepatocytes develop in setting of chronic hepatitis or cirrhosis

Genetics

• no genetic predisposition discernable
• overexpression of SMYD3, YY1AP1 common, PLXNB1
• lack of HTATIP2 expression in 33% of hepatocellular carcinomas
• PPAPDC1B may suppress metastases
• defects in MET are a cause of hepatocellular carcinoma
• other implicated genes GBA3, WDR16, HDMCP, RNF43, SULF1, DDEFL1, ANLN, HCC1, TBRG1, KIAA1524, GLOD4, HEPACAM, OIT3, PRAP1, MTUS1, PGCP, HEPN1, PHF19, PSMG2, PTPRH, CTNNB1, CCNDBP1, PEG10, DNCL2A, DYNLRB2, URG4, MICB, CDKN3, AXIN1

Clinical-manifestations

• abdominal pain
• malaise
• palpable liver mass
• stigmata of underlying cirrhosis or hepatitis
• may present as rapid deterioration in a patient with previously stable liver disease

Laboratory

• serum alpha-fetoprotein generally elevated (> 20 ng/mL)
• liver biopsy
• PCR/ southern blot/ northern blot
• autoantibodies: IGF2BP2, PHF20

Radiology

• abdominal ultrasound
• abdominal computed tomography ( CT)

• serum alpha-fetoprotein > 20 ng/mL
• abnormal abdominal ultrasound

Staging

• Barcelona Clinic Liver Cancer (BCLC) staging classification

• A asymptomatic early tumors suitable for resection, transplantation or percutaneous therapy
• B asymptomatic multinodular disease
• C symptomatic tumors &/or an invasive tumors pattern (vascular invasion/extrahepatic spread) candidates for palliative treatment, clinical trials
• D advanced disease, grim prognosis pallitative treatment only [3]

Complications

• 
  
• disease interaction(s) of cancer with Alzheimer's disease

Differential-diagnosis

• metastatic cancer
• regenerating liver nodule

Management

• surgical resection or liver transplantion as primary therapy [1]
• early identification & surgical resection

• after surgery, overall median survival is 45 months, 5-year survival is 39% [4]
• tumor size >2 cm, tumor multifocality, & presence of microvascular invasion predict poor prognosis [4]

• liver transplantation is generally associated with recurrence of tumor
• therapies with limited efficacy

• chemotherapy [1]
• arterial embolization
• radiotherapy
• intra-arterial & intratumoral injections

• progression to death within months is usual;

• overall survival at 3 years is only 5%

• screening of patients with cirrhosis

• periodic abdominal ultrasonography
• serum alpha-fetoprotein
• controversial

More General Terms

• adenocarcinoma
• liver neoplasm

Additional Terms

• aflatoxin B1
• alpha-fetoprotein (AFP) or alpha-1 fetoprotein
• androgen or anabolic steroid
• cirrhosis
• hemochromatosis
• hepatitis B virus (HBV)
• hepatitis C virus
• PCR/southern blot/northern blot for hepatocellular carcinoma

Internet Database

OMIM: 114550

References

1. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, American College of Physicians, Philadelphia 1998, 2006
2. N'Kontchou G et al, Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis Clin Gastroenterol Hepatol 2006, 4:1062 PMID: [1]
3. Llovet JM et al Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis. 1999;19(3):329-38. PMID: [2]
4. Nathan H et al Predictors of survival after resection of early hepatocellular carcinoma. Ann Surg 2009 May; 249:799. PMID: [3]
5. Liver Cancer:NIH Institute and Center Resources [4]
6. National Guideline Clearinghouse Management of hepatocellular carcinoma: an update. (American Association for the Study of Liver Diseases) ngc-guideline: [5]
   - The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer. (Program in Evidence-based Care) ngc-guideline: [6]
   - Sorafenib for the treatment of advanced hepatocellular carcinoma. National Institute for Health and Clinical Excellence (NICE) ngc-guideline: [7]

hepatocellular carcinoma