The document provides an overview of the Egyptian HCC Guidelines presented by Mohamed A. Ezzel Arab MD. It summarizes the guidelines on primary, secondary, and tertiary prevention of HCC. It also outlines recommendations for screening, diagnosis, staging, treatment including surgical resection, locoregional therapies, transplantation, and systemic therapies. Post-treatment monitoring guidelines are also presented. The document aims to provide evidence-based guidelines tailored to factors in Egypt based on international guidelines and expert opinion.

1. Egyptian HCC Guidelines
Overview
Presented By
Mohamed A. Ezzel Arab MD
Head of the HCC & Intervention Unit
National Hepatology & Tropical Medicine Research Institute
Treasurer of the Egyptian Society of Liver Cancer
(ESLC)

2. INTRODUCTION
ESLC invited most of experts with different
specialties in HCC management all over the country, to discuss the new
guidelines taking into consideration basically the international guidelines
(level I evidence based), and in parallel considering as well the local
factors in Egypt, in addition to their own experience
(level III, expert opinion) in those points which could not be applicable
in Egypt, provided that it is based on reliable international publications.
Confirmation and collecting these points were done using live
voting system.
The final draft had been completely endorsed by the ESLC to be applied
for the Egyptian HCC patients.

3. HCC EGYPTIAN GUIDELINES 2011
Primary Prevention
• Prevention of chronic HBV and HCV infection by:
- Safe injection practices.
- Screening of donated blood for the presence of hepatitis viruses.
Secondary Prevention
- Passive immunization with hyperimmune –globulin has a role
in preventing HBV after acute exposure.
- Antiviral therapeutic agents.
- Tertiery Prevention HBV is a valuable step in the prevention of
Immunization against
hepatocellular carcinoma.
- Avoid Aflatoxin B1 exposure.
-Prevention of dietary iron overload by westernization of the
cooking habits and tools.

4. HCC EGYPTIAN GUIDELINES 2011
Secondary Prevention
• Venesection for cases with high iron overload.
Tertiery Prevention
• Prevention of progression of the cirrhosis to HCC is done by treating the
hepatitis B and C virus infections .
• Preventing HCC caused by alcoholic cirrhosis by avoiding alcohol
• Prevention of Non alcoholic steato-hepatitis.

5. HCC EGYPTIAN GUIDELINES 2011
Screening Early detection of cases with hepatic nodule or elevated AFP
Diagnosis Accurate diagnosis of HCC
Staging Treatment decision making, and determining prognosis
Treatment Selection of appropriate therapy

6. HCC EGYPTIAN GUIDELINES 2011
Screening
Screening should be preformed to all high risk groups:
All cirrhotic patients: Non-cirrhotic patients:
HBV HBV infection (carrier)
HCV (Metavir score 3 or 4)
NASH
Alcoholic
Haemochromatosis
Screening for HCC should be done for all high risk patients with
AFP and abdominal U/S with time interval every 4 months

7. HCC EGYPTIAN GUIDELINES 2011
Diagnosis
Diagnosis should be made as follow:
High risk patient with HFL and either serum AFP is ≥ 200 ng/ml,
or triphasic CT-scan abdomen shows typical criteria for HCC
then, it has to be diagnosed as HCC.
(NB: Radiological criteria of HCC is in the form of early
enhancement during arterial phase followed by rapid
washout of contrast in delayed phase)

8. HCC EGYPTIAN GUIDELINES 2011
Diagnosis
Senario (1)
High risk patient with HFL < 1cm, AFP < 200 ng/ml, then
follow up every 2 months by abdominal U/S and serum
AFP is recommended. If the lesion increases in size
then, reassess with triphasic CT-scan abdomen
Senario (2)
High risk patient with HFL ≥ 1cm, AFP has normal level or
< 200 ng/ml and triphasic CT-scan abdomen shows
atypical criteria for HCC then, a dynamic contrast MRI
(with magnet strength≥ 1.5 tesla) is recommended. If MRI
is not available or its result is not satisfactory then
targeted liver biopsy is recommended.

9. HCC EGYPTIAN GUIDELINES 2011
Diagnosis
Senario (3)
High risk patient with serum AFP ≥ 200 ng/ml and no HFL
could be detected neither by abdominal U/S nor trisphasic
CT-scan abdomen then, a dynamic MRI study (≥ 1.5 tesla)
is recommended.

11. HCC EGYPTIAN GUIDELINES 2011
The recommended Workup for HCC patient at
time of diagnosis is:
- Full History (concerning the risk factor, occupation,
exposure to toxins, chemical …etc).
- Physical Examination.
- CBC.
- Bleeding profile (PT, INR and PTT).
- Liver function tests and LDH.
- Kidney function tests.
- AFP.
- Etiologies of liver cirrhosis: (HBsAg, HBcAb, HCV-Ab).
- ECG.
Triphasic spiral CT-scan abdomen or MRI ≥1.5 tesla
whenever indicated

12. HCC EGYPTIAN GUIDELINES 2011
Indications for HCC metastatic workup are:
• Clinical suspicion.
• Prior to transplant.
Screening for HCC metastasis is performed with:
• Chest/Pelvis CT with contrast.
• Bone scan on clinical suspicion or in symptomatic patients.

13. Staging of HCC
It should include the proper assessment of different views
covering; the patient clinical state, liver state, tumor size,
number, site, vascular invasion and extrahepatic disease.
Patient 1. Llovet JM. J Gastroenterol. 2005;40:225-235;
2. Marrero JA, et al. Clin Liver Dis. 2006;10:339-351;
3. Bruix J, et al. J Hepatol. 2001;35:421-430;
ECOG
PST
BCLC4
GRETCH5
Okuda6
Child-
Pugh CUPI7 TNM
CLIP8
JIS9
Liver Tumor

14. BCLC Staging System
HCC
Early Stage Intermediate Stage Advanced Stage End Stage
Surgical Treatment TACE Sorafenib
Local Ablation
(30%)
(50%-60%) (10%)
Potentially Curative
Randomized Trials BSC
Treatments 5-y
Median Survival If Untreated: 6-16 mo Survival <3 mo
Survival: 40%-70%
TACE = transarterial chemoembolization; BSC = best supportive care.
Llovet JM, et al. J Natl Cancer Inst. 2008;100:698-711.

15. HCC EGYPTIAN GUIDELINES 2011
Surgical Resection:
Patient who is fit for surgical resection should fulfill the
following conditions:
• Child Pugh score < 6 (Child A).
• Good performance status.
• Site is anatomically accessible(cases with subcapsular HCC
are good candidates for surgical resection while deep
lesions should be assessed first for the possibility of ablative
therapies).
• Serum bilirubin < 1.5 mg/dl.
• Localized HCC.
• No vascular invasion.
• Absence of extrahepatic spread (EHS).
• Absence of portal hypertension.

16. HCC EGYPTIAN GUIDELINES 2011
N.B: Criteria predicting portal hypertension are:
•Platelets count < 100,000 /mm3.
•Splenomegaly.
•Upper GIT endoscopy showing either esophageal varices or
signs of portal hypertensive gastropathy.
•Hepatic Venous Wedge Pressure (HVWP > 10 mmHg).
Large HCC lesion is not a contraindication for liver resection
provided an adequate residual volume of the cirrhotic liver after
proper metastatic workup.
N.B: operative theatres for liver surgery should be fully equipped
with all facilities and equipments required especially operative
ultrasound machine and capability of operative ablative therapy.

17. HCC EGYPTIAN GUIDELINES 2011

18. HCC EGYPTIAN GUIDELINES 2011
Liver transplantation will be beneficial for
recurrent HCC within Milan criteria after liver resection with
the following criteria:
•No micro-vascular invasion.
•Well differentiated HCC.
•Acceptable AFP < 1000 ng/ml.

19. HCC EGYPTIAN GUIDELINES 2011

20. HCC EGYPTIAN GUIDELINES 2011
In bridging or downstaging of HCC either by surgical
resection or locoregional therapy, liver transplantation
could be done if:
serum AFP is < 1000 ng/ml.
Adequate radiological response (Partial and complete
responders) according to modified RECIST criteria after
locoregional therapy.
Absence of disease progression during time period of 3
months.

21. HCC EGYPTIAN GUIDELINES 2011
Local recurrence of HCC after liver transplantation may be
treated with surgery if it is resectable
or with loco-regional therapy if it is unresectable.
While Sorafenib is the only available systemic therapy
indicated in distant recurrent HCC.

22. HCC EGYPTIAN GUIDELINES 2011
Locoregional Therapy:
HCC ≤ 4 cm, away from main bile ducts or intestinal loops,
without vascular invasion or extrahepatic spread in Child-
Pugh A or B patients neither candidate for surgery nor
ready for liver transplantation, are candidates for
Radiofrequency (RFA) or Microwave ablation.
HCC ≤ 4 cm close to a great vessel, without vascular
invasion or extrahepatic spread in Child-Pugh A or B
patients neither candidate for surgery nor ready for liver
transplantation, are candidates for Microwave ablation.

23. HCC EGYPTIAN GUIDELINES 2011
RFA and Microwave ablation are contraindicated in lesions
located in close contact with main bile ducts or intestinal
loops. So, the best clue for these patients with Child Pugh
Class A or B, neither fit for resection nor transplantation, is
Percutanous Ethanol Injection (PEI) in lesions < 3 cm or
combined Transarterial Chemoembolization (TACE) + PEI
for lesions 3 – 6 cm.
Also intra operative RFA could be an alternative for patient
who is fit for surgery with single HCC ≤ 4cm close to
intestinal loops.

24. HCC EGYPTIAN GUIDELINES 2011
HCC measuring 4 – < 6 cm, away from main bile
ducts or intestinal loops without vascular invasion or
extra-hepatic spread in Child A or B patient neither
candidate for surgery nor ready for transplantation, are
candidates for combined therapy of Heat ablation
(with RFA or Microwave ablation) + TACE.
HCC measuring ≥ 6 cm or multifocal lesions, without
vascular invasion or extra-hepatic spread in Child A and
early B and not candidate for surgical management, could
be treated with TACE.
Addition of Sorafenib is optional, to act against the rising
serum level of VEGF which occur especially during the
first week after embolization.

25. HCC EGYPTIAN GUIDELINES 2011
Ablation therapy could be performed as a potentially
curative modality for up to 3 lesions, however, cases
with more than 3 lesions are not an absolute
contraindication for ablation and should be discussed
on a case by case basis.

26. HCC EGYPTIAN GUIDELINES 2011
Single or multifocal HCC with portal vein invasion
in Child Pugh Class A or early B patient are candidates for
Sorafenib.
Furthermore, in respect to the rising promising data
coming to support the use of Selective Internal
Radiotherapy (SIRT) with Y-90 in advanced HCC especially
in case of portal vein thrombosis.
Radioembolization with Y-90 could be recommended as a
second line of treatment for those patients in the following
situations:
- Progressive disease inspite of full dose Sorafenib.
- Patient who can’t tolerate the adverse events of
Sorafenib.

27. HCC EGYPTIAN GUIDELINES 2011
Systemic treatment:
Sorafenib is the standard systemic therapy indicated for
treatment of HCC in the following conditions:
• Extrahepatic spread (such as lymph node, lung or suprarenal
metastasis).
• Vascular invasion (such as malignant portal vein or hepatic vein
invasion).
• In patients with post-transarterial chemoembolization (TACE)
progressive disease.
HCC patient who is candidate for Sorafenib should have
Child A liver cirrhosis or early B (score≤7), good
performance status, and serum bilirubin ≤ 2 mg/dl.
The standard daily oral dose of Sorafenib is 800 mg/day
(divided into two doses per day) one hour before meals or
two hours after meals.

28. HCC EGYPTIAN GUIDELINES 2011
Systemic treatment:
Clinical follow up of patients on Sorafenib should be performed
twice monthly after beginning of treatment then monthly on a
regular basis. While assessment of radiological response with
modified RECIST criteria is accepted with triphasic spiral CT-
scan or MRI (≥ 1.5 tesla) every three months.
Addition of external beam radiotherapy is amenable in case of
bone metastasis together with Sorafenib
Finally, ESLC is aware of the plethora of targeted therapies
that are in progress in phase II and III clinical trials.
Therefore in case of Sorafenib failure in patients who are still
maintaining child score A and good performance status, they
could be included into clinical trials.

29. HCC EGYPTIAN GUIDELINES 2011
Best Supportive Care:
It is the only line of treatment indicated for end stage HCC
which is defined by; poor performance score or child C liver
cirrhosis who are not eligible for transplantation.
Best supportive care should cover the following states:
• Treatment of portal hypertension.
• Nutritional management.
• Pain management.
• Psychological management.
• Control of ascites.

30. HCC EGYPTIAN GUIDELINES 2011
Post-therapeutic monitoring for HCC patients:
•Clinical:
Reassessment of the patient’s general condition and his Performance
status is mandatory.
•Serological:
•AFP (if elevated at baseline).
•CBC.
•LFTs (especially S. bilirubin).
•KFTs (especially S. uric acid).
•PT and INR
•Radiological:
It is recommended to perform tri-phasic CT-scan abdomen one
month after initial treatment, then every 3 months during the first
year after therapy. Then every 6 months if the patient does not
develop recurrence or disease progression ,meanwhile he should
enter in the screening program by abdominal U/S and serum AFP / 4
months ,aiming early detection of new HCC.

31. Close to
intestinal loops
Laparoscopic
RFA

34. THANK YOU