Clinical case presentation: HCC - Virology...
Transcript of Clinical case presentation: HCC - Virology...
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
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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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
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
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
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
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
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
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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Radiofrequency
14Presented 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
• 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
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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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
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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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
Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,
31 May – 2 June 2010, Tel Aviv, Israel
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••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
Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,
31 May – 2 June 2010, Tel Aviv, Israel
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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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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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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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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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
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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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
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
Presented at the 6th International Workshop on HIV & Hepatitis Co-infection,
31 May – 2 June 2010, Tel Aviv, Israel
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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
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