Hepatocellular Carcinoma

Overview

Overview Hepatocellular carcinoma (also known as hepatoma ) is a primary cancer arising from hepatocytes in predominantly cirrhotic liver. Hepatocellular carcinoma is a leading cause of death worldwide, and cirrhosis is the main risk factor. Infection with hepatitis B and hepatitis C is the main cause of underlying liver disease. Prevention of chronic liver disease would greatly reduce incidence. Early tumour diagnosis through screening of at risk groups is cost effective

Anatomy

The liver is wedge-shaped and is present in the right upper quadrant of the abdomen. The liver typically extends from the fifth intercostal space to the right costal margin in the midclavicular line.

A normal liver that is palpable
In thin people
During deep inspiration
In the setting of a right pleural effusion
When emphysema results in hyperinflation of the chest with diaphragmatic descent and downward displacement of the liver

 

Risk Factors

  • Older Age
  • Male gender
  • Hepatitis B infection
  • Hepatitis C infection
  • Alfatoxins (mycotoxins - fungal) - Alfatoxin B1 is a potent carcinogen
  • Non-alcoholic steatohepatitis (both independently and as a cofactor)
  • Diabetes
  • Family History of hepatocellular carcinoma

Signs and Symptoms

Differential Diagnosis

Differential diagnosis of a Firm and Palpable Liver History Clinical Feature
Hepatocellular carcinoma
Metastatic Disease
Cirrhosis
Sarcoidosis
Hydatis disease
Differential Diagnosis of a Tender liver History Clinical Feature
Hepatitis
Budd-Chiari Syndrome (hepatic vein thrombosis)
Hepatocellular carcinoma
Hepatic abscess
Biliary Obstruction/chonlangitis

 

DIFFERENTIAL DIAGNOSIS OF A PALPABLE LIVER
Massive Moderate Mild
Metastasis Massive causes Massive and Moderate causes
Hepatocellular Cancer Haemochromatosis Hepatitis
Alcoholic liver disease Haematological Disease Biliary obstruction
Myeloproliferative disease Secondary fatty liver disease (diabetes, obesity) Hydatid disease
Right-sided heart failure Amyloidosis HIV infection

Investigations and Diagnosis

General

  • FBC
  • EUC
  • LFT
  • Coagulation studies
  • Ultrasound
  • MRI
  • CT (with IV contrast)

Chronic liver disease screen

  • Hepatitis B surface antigen
  • Hepatitis C antibody
  • Liver autoantibodies
  • Immunoglobulins
  • Ferritin
  • alpha1-antitrypsin (also affects the lungs)
  • Caeruloplasmin

Other investigations for Differential Diagnosis

  • Amylase/lipase
  • CEA
Remember Screening with ultrasound for Hepatocellular carcinoma is recommended for patients with liver cirrhosis (as well as of other risk factors) every 6 months.

Pathology

Classification

Child-Pugh Score (Determines liver function)

 

 

Barcelona clinic liver cancer (BCLC) staging classification - to help guide management - looks at the following factors:

  • Performance status
  • Child-Pugh score (determines liver function)
  • Tumour size
  • Multiple tumours
  • Vascular invasion
  • Nodal spread and extrahepatic metastases
Barcelona clinic liver cancer Feature
Stage 0 (very early stage) Asymptomatic early tumours
Stage A (early stage) Asymptomatic early tumours
Stage B (intermediate stage) Asymptomatic multinodular tumours
Stage C (advanced stage) Symptomatic tumours and/or invasive tumours
Stage D (end-stage) Symptomatic treatment

Management

Barcelona clinic liver cancer (BCLC) staging classification - to help guide management - looks at the following factors:

  • Performance status
  • Child-Pugh score (determines liver function)
  • Tumour size
  • Multiple tumours
  • Vascular invasion
  • Nodal spread and extrahepatic metastases
Barcelona clinic liver cancer Feature Treatment
Stage 0 (very early stage) Asymptomatic early tumours Resection
Stage A (early stage) Asymptomatic early tumours Resection, percutaneous ablation, transplantation
Stage B (intermediate stage) Asymptomatic multinodular tumours Intra-arterial therapies (chemoembolisation and radioembolisation)
Stage C (advanced stage) Symptomatic tumours and/or invasive tumours Sorafenib, phase II trial agents, or palliative treatments
Stage D (end-stage) Symptomatic treatment

Treatment

  • Resection
  • Transplantation
  • Percutaneous treatment
    • Percutaneous ethanol injection
    • Radiofrequency ablation
  • Arterial embolization
  • Sorafenib
Pharmacology Sorafenib is indicated for the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. It is a multikinase inhibitor, by inhibiting these kinases, genetic transcription involving cell proliferation and angiogenesis is inhibited. Sorafenib has been shown to prolong survival and is regarded as the standard of care. The adverse reactions observed at this dose were primarily diarrhoea and dermatologic events

Complication and Prognosis

Complication

  • Biliary obstruction
  • Cachexia
  • Hypoglycemia
  • Hepatic failure
    • Varicose veins
    • Hepatic encephalopathy
    • Ascites
    • Peritonitis
    • Hepatrenal syndrome
  • Watery diarrhoea
  • Paraneoplastic syndrome - Hypercalcaemia
  • Intraperitoneal bleeding due to tumour rupture

Prognosis Hepatoma is a very aggressive tumour. The clinical course and survival depends upon the stage and overall functional status of the liver

Barcelona clinic liver cancer Feature Prognosis
Stage 0 (very early stage) Asymptomatic early tumours -
Stage A (early stage) Asymptomatic early tumours 50-70% 5 year survival with treatment
Stage B (intermediate stage) Asymptomatic multinodular tumours 50% 3 year survivial without treatment
Stage C (advanced stage) Symptomatic tumours and/or invasive tumours 50% 6 month survival
Stage D (end-stage) Symptomatic treatment 50% <3month survival

References

BestPractice
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