Clinical case presentation: HCC - Virology...

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Foundation Foundation I.R.C.C.S. I.R.C.C.S. San Matteo Hospital San Matteo Hospital - - University University of of Pavia, Italy Pavia, Italy Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious Diseases - Hepatology Outpatient Unit 1 Presented at the 6 th International Workshop on HIV & Hepatitis Co-infection, 31 May – 2 June 2010, Tel Aviv, Israel

Transcript of Clinical case presentation: HCC - Virology...

Page 1: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

FoundationFoundation I.R.C.C.S.I.R.C.C.S. San Matteo Hospital San Matteo Hospital -- UniversityUniversity ofof Pavia, ItalyPavia, Italy

Clinical case presentation: HCC

Raffaele Bruno,MDDepartment of Infectious Diseases - Hepatology Outpatient Unit

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 2: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

P.S. Gender: Male Year of Birth: ’64

Family History : lack of hereditary diseases

Alcohol intake: ≤ 20 gr/die

Clinical History:

Anti - HIV and HBsAg reactive in 1997

Risk factor for HIV & HBV : IVDU

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Page 3: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

P.S. Gender: Male Year of birth: ’64

Virologic and biochemical profile:

Status: HIV pos ; HBsAg pos; HBcAb pos; HBeAg neg - HBeAb pos;

HCV- HDV neg

Biochemistry : • persistent Alt elevation, without “flares”

(ALT> 300 U/l)• Total serum albumin 2.6 gr/dl• INR: 2.1 • Total bilirubin 2.5 mg/dlThe patient refused every kind of ARV therapy until

• November 2008 - CD4 208/mmc. HIV-RNA = 34.000 UI/ml. • ALT 4/5 times above upper limit HBV DNA 7.000.000 I.U./ml

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

The patient was started on ARV with TDF-FTC - FAPV/rtv (1400/100)

After 4 weeks he was admitted to the Hospital with

• Jaundice (Total bilirubin 6.1 mg/dl)

• Ascites Moderate, ALT 246 UI/ml

• Total serum albumin 2.6 gr/dl

• INR 3.2• No encephalopathy• US scan : ascites Moderate, splenomegaly , no focal lesions.• no resistance for HBV• Child Turcotte Pugh grading = C13

The patients was treated with Dietary NA+ restriction

Furosemide 40mg/die + Spironolactone 200 mg/die with recovery of the clinical signs in

2 weeks.

P.S. Gender: Male Year of birth: ’64

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

P.S. Gender: Male Year of birth: ’64

• The patient was maintained on ARV with TDF-FTC -FAPV/rtv ( the

dosage was adjusted by TDM ) (900/100)

• After six months the patients was clinically stable without evidence of

decompensationFollow up:

•ALT 135 UI/ml; •Total serum albumin 3.1 gr/dl; •Total Bilirubin 2.8 gr/dl•INR 2.1•No Ascites No encephalopathy •HIV-RNA 1500 UI/ml – CD4=303/mmc•HBV-DNA < 100 IU/ml

•Child Turcotte Pugh grading=B7•HVPG (hepatic venous pressure gradient) 12 mmHg

•US scan: HCC Ø 2,5 cm VIII seg – spleen enlargement

•Contrast-enhanced spiral CT : confirm the diagnosis5

Page 6: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

US and CT scan: HCC Ø 2,5 cm VIII seg

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 7: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

HVPG IS INCREASED IN SINUSOIDAL PORTAL HYPERTENSIONHVPG IS INCREASED IN SINUSOIDAL PORTAL HYPERTENSIONHVPG IS INCREASED IN SINUSOIDAL PORTAL HYPERTENSION

Sinusoidalpressure = 20 mmHg

Sinusoidalpressure = 20 mmHg

Sinusoidalpressure = 20 mmHg

Blocked inter-sinusoidal communications(poor pressure dissipation)

Blocked inter-sinusoidal communications(poor pressure dissipation)

Blocked inter-sinusoidal communications(poor pressure dissipation)

Portal veinPVP = 20 mmHg

Portal veinPVP = 20 mmHg

Portal veinPVP = 20 mmHg

Hepatic veinsHepatic veinsHepatic veins

WHVP = 20 mmHgWHVP = 20 mmHgWHVP = 20 mmHg

FHVP = 2 mmHg

FHVP = 2 mmHg

FHVP = 2 mmHg

HVPG = 18 mmHg

HVPG = 18 mmHg

HVPG = 18 mmHg

HVPG is Increased in SinusoidalPortal Hypertension

HVPG is Increased in SinusoidalPortal Hypertension

HVPG is Increased in SinusoidalPortal Hypertension

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

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Portal Pressure MeasurementsPortal Pressure MeasurementsPortal Pressure Measurements

Definitive method to establish the diagnosis of portal hypertension

Direct methods (percutaneous, transjugular) are cumbersome and may be associated with complications

The safest and most reproducible method is measurement of the hepatic venous pressure gradient (HVPG)

Definitive method to establish the diagnosis of portal hypertension

Direct methods (percutaneous, transjugular) are cumbersome and may be associated with complications

The safest and most reproducible method is measurement of the hepatic venous pressure gradient (HVPG)

Definitive method to establish the diagnosis of portal hypertension

Direct methods (percutaneous, transjugular) are cumbersome and may be associated with complications

The safest and most reproducible method is measurement of the hepatic venous pressure gradient (HVPG)

PORTAL PRESSURE MEASUREMENTSPORTAL PRESSURE MEASUREMENTSPORTAL PRESSURE MEASUREMENTS

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

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Question 1

• What is the optimal management for this patient?1. Surgical resection2.Liver transplantation3.Radio frequency ablation (RF) o Percutaneous

Ethanol injection (PEI)4.Chemoembolization5.Therapy with Sorafenib

Page 10: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Very early stage (0) Single< 2cm.

Carcinoma in situ

Portal pressure < 10/ bilirubin

Okuda 3, PST >2, Child-Pugh C

Terminal stage (D)

Okuda 1-2, PST 0-2, Child-Pugh A-BStage A - C Stage D

Normal

Single 3 nodules <3cm

Associated diseasesIncreased

No Yes

Early stage ( A)Single or 3 nodules < 3cm, PS 0

Intermediate stage ( B)Multinodular, PS 0

Advanced stage (C)Portal invasion, N1,M1, PS 1-2

Portal invasion, N1,M1

No Yes

Stage 0PST 0, Child-Pugh A

Modified Llovet JM, Burroughs A, Bruix J. Lancet, 2003

BCLC Staging and Treatment Strategy HCC

Liver Transplantation (CLT / LDLT)

Chemoembolization SorafenibResection RFTA

Symptomatic treatment

Curative Treatments50% - 75% at 5 years

Randomized controlled trials40% - 50% at 3 yr vs 10% at 3yr

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FoundationFoundation I.R.C.C.S.I.R.C.C.S. San Matteo Hospital San Matteo Hospital -- UniversityUniversity ofof Pavia, ItalyPavia, Italy

EARLY-STAGE HCC: SURGERY AND TRANSPLANTATION• Surgical resection

– suitable for patients with solitary tumours and well-preserved liver function with HVPG < 10 mmHg

– 5-year survival: 60–70%– >70% of patients experience recurrence at 5 years– adjuvant therapy unproven

• Liver transplantation– appropriate for patients not suitable for resection – 5-year survival: ~70%– graft rejection and viral re-infection can be problematic

Llovet JM. J Gastroenterol 2005;40:225–35; Bruix J, Sherman M. Hepatology 2005;42:1208–36

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 12: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

FoundationFoundation I.R.C.C.S.I.R.C.C.S. San Matteo Hospital San Matteo Hospital -- UniversityUniversity ofof Pavia, ItalyPavia, Italy

EARLY-STAGE HCC: PEI AND RFA

• Performed in patients who are not suitable for surgery

• Chemical or thermal ablation induces tumour cell necrosis

• PEI is widely used– best outcomes seen in Child–Pugh A patients with single tumours <3cm

diameter (5-year survival 40–50%)

• RFA provides better disease control and survival than PEI in patients with tumours >2cm diameter, but is associated with more complications– comparable efficacy to resection, with superior tolerability

Llovet JM. J Gastroenterol 2005;40:225–35; Bruix J, Sherman M. Hepatology 2005;42:1208–36;Chen MS, Li JQ, Zheng Y, et al. Ann Surg 2006;243:321–8

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 13: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

P.S. Gender: Male Year of birth: ’64

• The patient was not eligible for resection because he was in Child B stage and HVPG >10 mmHg

• Upper digestive endoscopy showed varices F2and was started prophilaxys with propanolole

• He underwent a RFTA (Radiofrequency thermal ablation) which is a bridging strategy for OLT

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Page 14: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Radiofrequency

14Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 15: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

P.S. Gender: Male Year of birth: ’64

• He was included on the waiting list for liver transplantation

• 5 weeks after RFTA the Spiral CT demonstrated the complete necrosis of the nodule.

15Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 16: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

•The Patient entered a 3 months US surveillance program

• After 3 months the contrast enhanced US did not demonstrate the recurrence of HCC .

• At the next US scan presence of multiple (>3) nodular lesions variable in size suggestive for multinodular HCCThis finding was confirmed by spiral CT

Child Turcotte Pugh grading =B7

P.S. Gender: Male Year of birth: ’64

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Page 17: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

HCC multifocal arterial fase

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

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Question 1

• What is the optimal management for this patients?

1. Surgical resection2.Liver transplantation3.Radio frequency ablation (RF) o Percutaneous

Ethanol injection (PEI)4.Chemoembolization5.Therapy with Sorafenib

Page 19: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Very early stage (0) Single< 2cm.

Carcinoma in situ

Portal pressure/ bilirubin

Okuda 3, PST >2, Child-Pugh C

Terminal stage (D)

Okuda 1-2, PST 0-2, Child-Pugh A-BStage A - C Stage D

Normal

Single 3 nodules <3cm

Associated diseasesIncreased

No Yes

Early stage ( A)Single or 3 nodules < 3cm, PS 0

Intermediate stage ( B)Multinodular, PS 0

Advanced stage (C)Portal invasion, N1,M1, PS 1-2

Portal invasion, N1,M1

No Yes

Stage 0PST 0, Child-Pugh A

Modified Llovet JM, Burroughs A, Bruix J. Lancet, 2003

BCLC Staging and Treatment Strategy HCC

Liver Transplantation (CLT / LDLT)

Chemoembolization SorafenibResection PEI/RF

Symptomatic treatment

Curative Treatments50% - 75% at 5 years

Randomized controlled trials40% - 50% at 3 yr vs 10% at 3yr

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Page 20: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

FoundationFoundation I.R.C.C.S.I.R.C.C.S. San Matteo Hospital San Matteo Hospital -- UniversityUniversity ofof Pavia, ItalyPavia, Italy

ADVANCED HCC: TRANS-ARTERIAL CHEMO-EMBOLISATION (TACE)

• TACE is widely used to treat unresectable, non-metastatic HCC

• Only benefits patients with preserved liver function and asymptomatic multinodular tumours without vascular invasion or metastases (~30% of patients)

• Embolisation agents may be administered alone or following intra-arterial chemotherapy

• TACE is often associated with side effects and may induce liver failure in patients with suboptimal hepatic function

Llovet JM. J Gastroenterol 2005;40:225–35

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 21: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

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Page 22: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

••Tumor vessels 25Tumor vessels 25μμm m --7575μμm diameterm diameter••End arterioles to venous 8End arterioles to venous 8--20 20 μμm diameterm diameter

suitable vehicles for selective delivery of very high radiation doses to tumors while radiation exposure to the normal hepatic parenchyma remains within tolerable limits

Rationale for Rationale for RadioembolizationRadioembolization

MicrospheresMicrospheres: 20: 20--40 40 µµmm

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 23: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 24: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

•The patient underwent 2 chemoembolizationprocedures.

•Follow-up CT scans were obtained approximately 15 days after the procedure. A dense opacificationassociated with necrosis was seen in the tumor.

•Follow-up CT scan obtained 3 months later showed complete resolution of the liver tumors.

P.S. Gender: Male Year of birth: ’64

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Page 25: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Transarterial embolization for HCC

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Page 26: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

CT after chemoembolization

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Page 27: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

After six months he underwent a CT scan showing a nodular lesion in V seg with Portal vein thrombosis.

P.S. Gender: Male Year of birth: ’64

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Page 28: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

28

Question 1

• What is the optimal management for this patients?

1. Surgical resection2.Liver transplantation3.Radio frequency ablation (RF) o Percutaneous

Ethanol injection (PEI)4.Chemoembolization5.Therapy with Sorafenib

Page 29: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Very early stage (0) Single< 2cm.

Carcinoma in situ

Portal pressure/ bilirubin

Okuda 3, PST >2, Child-Pugh C

Terminal stage (D)

Okuda 1-2, PST 0-2, Child-Pugh A-BStage A - C Stage D

Normal

Single 3 nodules <3cm

Associated diseasesIncreased

No Yes

Early stage ( A)Single or 3 nodules < 3cm, PS 0

Intermediate stage ( B)Multinodular, PS 0

Advanced stage (C)Portal invasion, N1,M1, PS 1-2

Portal invasion, N1,M1

No Yes

Stage 0PST 0, Child-Pugh A

Modified Llovet JM, Burroughs A, Bruix J. Lancet, 2003

BCLC Staging and Treatment Strategy HCC

Liver Transplantation (CLT / LDLT)

Chemoembolization SorafenibResection PEI/RF

Symptomatic treatment

Curative Treatments50% - 75% at 5 years

Randomized controlled trials40% - 50% at 3 yr vs 10% at 3yr

29

Page 30: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

FoundationFoundation I.R.C.C.S.I.R.C.C.S. San Matteo Hospital San Matteo Hospital -- UniversityUniversity ofof Pavia, ItalyPavia, Italy

SORAFENIB ACTS BY BLOCKING Tyrosin kinase AND TARGETS PROLIFERATION AND ANGIOGENESIS OF

HCC

Angiogenesis

Raf

Endothelial cell or pericyte

Nucleus

VEGFR-2PDGFR-β

MEKApoptosis

Tumour cell

Proliferation

PDGFVEGF

EGF

Survival

Ras

Nucleus

Ras

ERK

Raf

MEKApoptosis

ERK

PDGF-β VEGFParacrine stimulation

sorafenib

KIT/Flt-3/ RET

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 31: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

Potential Pharmacological Interaction between Sorafenib and

AntiretroviralsUse with care and if possible avoid:

•NNRTI (possible sorafenib concentration reduction)

•Tenofovir (possible additional Hypophosphataemia effect)

• Use with caution the PI (TDM)

31Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

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Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

32

He started SORAFENIB therapy 400mg BID

He had some common side effects Sorafenibrelated:

Diarrhea

HFSR = hand-foot skin reaction

So far, the patient is still on treatmentwith a reduced dose of sorafenib.

P.S. Gender: Male Year of birth: ’64

Page 33: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious

The HCC Doc’s “wish list”Robust biomarkers to:

- predict who will develop HCC- identify high risk subjects- detect HCC at a premalignant stage

- define clusters of homogeneous tumors - discriminate displasia from early HCC

- predict evolution - predict treatment outcomes- predict recurrence after treatment

Prognosis

Early diagnosis

Screening/prevention

DiagnosisClassification

Early referring to transplant center !!!Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,

31 May – 2 June 2010, Tel Aviv, Israel

Page 34: Clinical case presentation: HCC - Virology Educationregist2.virology-education.com/6thCoinf/docs/10_Bruno.pdf · Clinical case presentation: HCC Raffaele Bruno,MD Department of Infectious