Tumor incidence varies significantly, depending on geographical location.

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2 Hepatocellular carcinoma is the 5 th most common malignancy worldwide with male-to-female ratio 5:1 in Asia 2:1 in the United States Tumor incidence varies significantly, depending on geographical location. HCC with age. 53 years in Asia 67 years in the United States.

3 Incidence according to etiology

4 Etiology Hepatitis B -increase risk fold Hepatitis C Cirrhosis - 70% of HCC arise on top of cirrhosis Toxins -Alcohol -Tobacco - Aflatoxins Autoimmune hepatitis States of insulin resistance- Overweight in males Diabetes mellitus

5 Signs & symptoms Nonspecific symptoms Physical findings abdominal pain Fever, chills anorexia, weight loss jaundice abdominal mass in one third splenomegaly ascites abdominal tenderness

6 which patients are at high risk for the development of HCC & should be offered surveillance - M &F with established cirrhosis due to HBV and/ or HCV, particularly those with ongoing viral replication - M &F with established cirrhosis due to genetic haemochromatosis - M with alcohol related cirrhosis - M with primary biliary cirrhosis

7 Patient who require surveilance Asian men > 40 y (HBV chronic hepatitis) Asian women> 50 y Family history of Hcc Cirrhotic patient African and and north American black

8 Screaning Patient with hbv who are African appear to get hcc at a younger age

9 Risk factor for hbv Host Male ( estrogen and testosterone ) Family history of hcc Cirrhosis obesity

10 virus Elevated hbv DNA level Hbe Ag Genotype C and D HDV, HIV, or HCV co-infection

11 Environmental Alcohol Tobacco ( smoking) Aflatoxin B

12 Because hcc may develop in chronic hbv in the absence of cirrhosis, many patients may have had preserved liver function and thus been able to tolerate resection.

13 hcc Genotype 1b HCV RNA level

14 diagnosis Ultra sonography AFP

15 End stage of cirrhosis(prognosis)

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17 Treatment/Managmenttement

18 Treatment (Surgery) The only proven potentially curative therapy for HCC Hepatic resection or liver transplantation Patients with single small HCC ( 5 cm) or up to three lesions 3 cm

19 Resection Hepatic resection should be considered in HCC and a noncirrhotic liver (including fibrolamellar variant) Resection can be carried out in highly selected patients with cirrhosis and well preserved hepatic function (Child- Pugh A) who are unsuitable for liver transplantation. It carries a high risk of postoperative decompensation. The majority of early mortality is due to liver failure.

20 Transplantation Liver transplantation should be considered in any patient with cirrhosis

21 Transplantation Milan Criteria : Single HCC 5 cm or Up to three nodules 3 cm No extra hepatic spread About 10 % qualify for listing The major drawback of transplantation is The scarcity of donors. The long waiting time.

22 Treatment (non-surgical) should only be used where surgical therapy is not possible. 1) Percutaneous ethanol injection (PEI) has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3 cm in diameter 2) Radiofrequency ablation (RFA) High frequency ultrasound to generate heat good alternative ablative therapy No survival advantage Useful for tumor control in patients awaiting liver transplant

23 Treatment (non-surgical 3) Cryotherapy intraoperatively to ablate small solitary tumors outside a planned resection in patients with bilobar disease 4) Chemoembolisation Concurrent administration of hepatic arterial chemotherapy (doxirubicin) with embolization of hepatic artery Produce tumour necrosis in 50% of patients Effective therapy for pain or bleeding from HCC Affect survival in highly selected patients with good liver reserve Complications: (pain, fever and hepatic decompensation)

24 Treatment (non-surgical 5) Systemic chemotherapy very limited role in the treatment of HCC with poor response rate Best single agent is doxorubicin (RR: 10-20%) should only be offered in the context of clinical trials 6) Hormonal therapy - Nolvadex, stilbestrol and flutamide 7) Interferon-alfa 8) retinoids and adaptive immunotherapy (adjuvant)

25 Radiofrequency Ablation

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27 Transarterial Chemoembolization Meta-analysis of 7 randomized controlled trials 2 yr survival: 41% (19-63%) Treatment response: 35% (16-61%) Average no. of sessions: Risks: Infection Tumor lysis syndrome Hepatic failure