HCC Clinical update and hints from AASLD 2017 guidelines mainly about surveillance, diagnosis and treatment of Hepatocellular carcinoma in different stages.

1. HCC: Clinical Updates
Ahmed ElMoughazy
Internal Medicine, Hepatology Unit, Medical Research Institute, Alexandria University.

2. HCC: A growing problem…
 Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy of adults.
 It is the sixth most common cancer worldwide and the third most common cause of cancer
death.
 HCC constitutes 70% of all liver tumors among Egyptians.
 HCC represents the main complication of cirrhosis, and shows a growing incidence in Egypt.

3. 2008 Global Cancer Incidence
This graphic shows the global incidence of the most common cancers in in 2008. Overall, an estimated 12.7 million new
cancers occurred globally in the year 2008. Approximately 750,000 persons had a diagnosis of HCC in 2008.

4. 2008 Global Cancer Deaths
This graphic shows the number of global cancer deaths, by type of cancer in 2008. Approximately 700,000 persons died of
HCC in 2008.

5. HCC Risk Factors
HBV
HCV
Alcohol
Cirrhosis
Age peak (50-70 years)
Gender (male 2-4 times > female)
Others: Alfatoxin B1, Hemochromatosis

6. Progression to HCC from HCV-
related Cirrhosis

7. HCC
Clinical Presentations
 Median age 40-50 years
 Men to women 2-4:1
 40% asymptomatic
 Pain occurs with invasion of Glisson’s capsule
 Rupture into the peritoneum (5%)
 Manifestation of liver cirrhosis
 Wasting in only 15%
 Fever in 40%
 Bloody ascites

8. AASLD Diagnostic Algorithm for Suspected
HCC Identified on Ultrasound
Abbreviations: CT = computed tomography; MDCT = multidetector CT; MRI = magnetic resonance imaging; US = ultrasound
Source: Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma:
an update. Hepatology. 2011;53:1020-2.

9. Alpha Fetoprotein (AFP):
 Sensitivity of only 47 to 64% and a specificity of 82 to 95% for detecting HCC among HCV-
infected patients.
 The poor sensitivity primarily results from the lack of uniform secretion of AFP by HCC tumors
and AFP level.
 AFP is no longer recommended as a routine surveillance test. If there is uncertainty about an
imaging study and a biopsy cannot be performed, then AFP might provide useful additional
information.

10. Des-gamma-Carboxy Prothrombin (DCP):
 The protein DCP is an abnormal prothrombin molecule generated as a result of an acquired
defect in the carboxylation of the prothrombin precursor in malignant cells.
 In a large study involving HCV-infected patients with cirrhosis, investigators examined DCP, AFP,
and the combination of DCP and AFP, but none of these strategies showed adequate sensitivity
to justify the use of DCP as a routine surveillance test.
 In contrast, DCP may have some utility as a marker of advanced HCC.

11. Impact of Screening on Stage of HCC at
Time of Diagnosis
In a trial performed in Shanghai, China, more than 18,000 persons with chronic viral hepatitis (most of who had chronic hepatitis B),
were randomized to screening for HCC or no screening (control). As shown, individuals who received screening were more likely to
have their HCC diagnosed at an earlier stage (Stage 1) than those who did not have screening.

12. Impact of Screening on Survival after
Diagnosis of HCC
In this trial, patients with chronic viral hepatitis who underwent screening for HCC had improved survival after the diagnosis
of HCC when compared with the control group that did not receive screening for HCC.

13. 13
Barcelona Clinic Liver Cancer
Proposed Treatment Algorithm
AASLD Guidelines. Bruix J and Sherman M. Hepatology 2005;42:5:1208-1222.

15. Child – Pugh Score

16. Okuda Staging system
The Okuda staging system was an advance on earlier hepatocellular (HCC) staging
classifications, in that it incorporated both cancer-related variables and liver function related
variables to determine prognosis :
 disease involving >50% of hepatic parenchyma
 ascites
 albumin ≤3 mg/dL
 bilirubin ≥3 mg/dL
These are combined into stages:
 stage A: 0 criteria
 stage B: 1-2 criteria
 stage C: 3-4 criteria

18. Highlights on AASLD
Guidelines 2017
Official recommendations of the
American Association for the Study
of Liver Diseases (AASLD) on the
surveillance, diagnosis, and
treatment of hepatocellular
carcinoma (HCC) occurring in the
setting of adults with cirrhosis.

19. SHOULD ADULTS WITH CIRRHOSIS UNDERGO SURVEILLANCE
FOR HCC, AND IF SO, WHICH SURVEILLANCE TEST IS BEST?
The AASLD suggests not performing
surveillance of patients with cirrhosis with
Child’s class C unless they are on the
transplant waiting list, given the low
anticipated survival for patients with Child’s
C cirrhosis.

20. SHOULD ADULTS WITH CIRRHOSIS AND SUSPECTED HCC UNDERGO
DIAGNOSTIC EVALUATION WITH MULTIPHASIC CT OR MULTIPHASIC MRI?
The AASLD recommends diagnostic
evaluation for HCC with either multiphasic
CT or multiphasic MRI because of similar
diagnostic performance characteristics.

21. SHOULD ADULTS WITH CIRRHOSIS AND AN INDETERMINATE HEPATIC
NODULE UNDERGO A BIOPSY, REPEATED IMAGING, OR ALTERNATIVE
IMAGING FOR THE DIAGNOSTIC EVALUATION?
AASLD suggests against routine biopsy of
every indeterminate nodule

22. SHOULD ADULTS WITH CHILD’S CLASS A CIRRHOSIS AND EARLY-STAGE
HCC (T1 OR T2) BE TREATED WITH RESECTION OR LOCOREGIONAL
THERAPY?
The AASLD suggests that adults with
Child’s A cirrhosis and resectable T1 or T2
HCC undergo resection over
radiofrequency ablation.

23. SHOULD ADULTS WITH CIRRHOSIS AND HCC THAT HAS BEEN RESECTED
OR ABLATED SUCCESSFULLY UNDERGO ADJUVANT THERAPY?
The AASLD suggest against the routine use of adjuvant
therapy for patients with HCC following successful resection or
ablation.
Of the agents evaluated in the adjuvant setting, only sorafenib
has been shown to improve survival in advanced disease.

24. SHOULD ADULTS WITH CIRRHOSIS AND HCC WHO ARE NOT CANDIDATES FOR
RESECTION OR TRANSPLANTATION BE TREATED WITH TRANSARTERIAL
CHEMOEMBOLIZATION, TRANSARTERIAL RADIOEMBOLIZATION, OR EXTERNAL
RADIATION?
The AASLD does not recommend one form of
LOCOREGIONAL THERAPY (LRT) over another

25. SHOULD ADULTS WITH CHILD–PUGH A/B CIRRHOSIS AND ADVANCED HCC
WITH MACROVASCULAR INVASION AND/OR METASTATIC DISEASE BE TREATED
WITH SYSTEMIC OR LOCOREGIONAL THERAPY (LRT) OR NO THERAPY?
The AASLD recommends the use of systemic
therapy over no therapy for patients with Child–
Pugh A cirrhosis or well-selected patients with
Child’s B cirrhosis plus advanced HCC with
macrovascular invasion and/or metastatic
disease.

26. SHARP TRIAL (Sorafenib
Hepatocellular Carcinoma
Assessment Randomized
Protocol )
 Sorafenib significantly improved
the median overall survival in:
 The entire population included in
the study (sorafenib 10.7 months
versus placebo arm 7.9 months)
 In patients with macrovascular
invasion (sorafenib 8.1 months
versus placebo arm 4.9 months)
 In patients with metastatic
disease (sorafenib 8.9 months
versus placebo arm 8.3 months)