Assessment of Liver Function: Implications for HCC Treatment

Transcription

1 Assessment of Liver Function: Implications for HCC Treatment A/P Dan Yock Young MBBS, PhD, MRCP, MMed. FAMS Chair, University Medicine Cluster. NUHS Head, Department of Medicine, National University of Singapore, Head & Senior Consultant. Dept of Gastro/Hepatology. Adjunct. Cancer Science Institute National University Singapore. Clinical Care Education Research

2 Patients with HCC Age 46 years old Presented with abdominal swelling Multifocal HCC Treated with SIRT Progressed and went on sorafenib Died at 14 months. Survival of HCC Greten BJC 2000

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4 Signaling Mechanism in HCC Hanahan Cell 2000

5 Metanalysis of gene expression profile of HCC: 8 dataset.n=600 Hoshida Y, et al. Cancer Res Lee. Nat Med 2005

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8 Liver function and impact on survival Treatment and impact on liver reserve How to assess Liver Function Liver function and impact on treatment

9 Liver Function and impact on survival How to assess Liver Function Liver Function and impact on Treatment Liver Function and impact of Treatment Liver Function and-cost Effectiveness of Rx

10 Pathogenesis of HCC Farazi and DePinho Nature Reviews Cancer 2006

11 Pathogenesis of HCC Farazi and DePinho Nature Reviews Cancer 2006 Patients with HCC also have Liver cirrhosis and are more likely to die of complications of liver cirrhosis including bleeding, sepsis, HRS other than direct complications of HCC rupture, PVT related variceal bleed or metastasis

12 Survival of cirrhotic patients G. D Amico et al. / Journal of Hepatology 44 (2006)

13 Survival of compensated vs decompensated cirrhotic patients

14 Liver Function and Impact on Survival Molecular signature of tumour does not correlate with overall survival. Instead the signature of surrounding tissue did. HCC Molecular Signature Surrounding tissue moelcular signature Hoshida. NEJM. 2008

15 Liver function and impact on survival Treatment and impact on liver reserve How to assess Liver Function Liver function and impact on treatment

16 Liver Reserve and threshold

17 The functional liver reserve Capacity Synthetic function Excretion Detoxification Demand Catabolic and Anabolic needs of the body Normal person needs 30% of liver to meet the metabolic needs of the body * The liver regenerated rapidly when demand exceeds supply

18 The functional liver reserve Capacity Synthetic function Excretion Detoxification Demand Catabolic and Anabolic needs of the body In diseased liver, the liver s regenerative capacity is limited. Increase in metabolic needs of the body will result in insufficient liver reserve To meet the needs liver failure

19 Collateral Damage with Treatment Capacity Synthetic function Excretion Detoxification Demand Catabolic and Anabolic needs of the body

20 Defining where the liver reserve is? Estimate whether the cirrhosis or the HCC will be the limiting factor Minimum liver function Survival

21 Capacity Synthetic function Excretion Detoxification Demand Catabolic and Anabolic needs of the body Surgery TACE especially if PVT SIRT if large tumours RFA Sorafenib

22 Liver function and impact on survival Treatment and impact on liver reserve How to assess Liver Function Liver function and impact on treatment

23 Liver Function Test Test Measure Liver Function Test TB/ Albumin Function ALT/ AST Injury Prothrombin Time PT Synthetic Fibrosis Fibroscan Fibrosis MRE Ultrasound Fibrosis Cirrhosis ICG ICG15 Liver perfusion/ shunt/ sinusoid Breath test C13 aminopyrine Microscomal fn Radioactive scintigraphy C13 methacetin technetium-99 m galactosyl human serum albumin Metabolism

24 Child-Pugh Score

25 MELD MELD = 3.78[Ln serum bilirubin (mg/dl)] [Ln INR] [Ln serum creatinine (mg/dl)]

26 Liver function and impact on survival Treatment and impact on liver reserve How to assess Liver Function Liver function and impact on treatment

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28 AASLD guideline 2010 Recommendation 10. To best assess the prognosis of HCC patients it is recommended that the staging system take into account tumour stage, liver function and physical status. The impact of treatment should also be considered when estimating life expectancy.

29 Variables Used in HCC Staging Systems System Tumor Staging Liver Function Health Status Europe-US GETCH/ French PVT; AFP < 35 or > 35 ug/l Bilirubin, alkaline phosphatase Karnofsky CLIP Number of nodules, tumor > or < 50% area of liver, and PVT; AFP< 400 or 400 ng/ml CTP No BCLC Tumor size, number of nodules, and PVT CTP PST TNM Number of nodules, tumor size, presence of PVT, and presence of metastasis No No Asia JIS TNM CTP No Okuda/ Tokyo Tumor > or < 50% of cross-sectional area of liver Ascites, albumin, and bilirubin No CUPI TNM; AFP< 500 or 500 ng/ml Bilirubin, ascites, alkaline phosphatase Symptoms Marrero JA, et al. Hepatology. 2005;41:

30 1. Liver Resection- Hepatic Insufficiency Can the patient survive the surgery? Risk Factors for decompensation/ death Child Pugh classification >A Decompensation Increased Bilirubin Portal Hypertension fluid retention requiring diuretic therapy.217 Presence of varices splenomegaly and thrombocytopenia Hepatic vein catheterization hepatic vein pressure gradient <10 mmhg) Indocyanine Green retention test Normal bilirubin No PHT Normal bil PHT Raised Bil PHT Multifocal Decomp low Likely Usually 5YS >70% 50% <30% Huo et al Am J Gastroenterol 2007 OIshizawa et al. Gastroenterology 2008

31 Indocyanine Green retention test Measure of hepatic blood flow, sinusoidal capillarisation, intrahepatic portovenous shunt ST Fan 2009

32 Liver Transplant Unsafe for resection MELD score >14 CPS B High risk of de novo recurrence

33 TACE and impact on liver function Importance of HA supply in cirrhosis due to portal hypertension PVT relatively contraindicated Highly selective catheterisation

34 TACE and impact on liver function Post-TACE liver failure occurred in 17 (17.3%) of 98 patients with HCC Poor Prognostic factors Ascites (RR)=1.75, P=0.004]. (Cox proportional hazard model) Child-Turcotte-Pugh class B (odds ratio=10.1, P=0.038) Post-TACE gastrointestinal bleeding (odds ratio=10.86, P=0.006) Hsin et al. J Clin Gastroenterol 2011

35 Ablative Treatment Localised Complications predisposing to decompensation catabolic state Sterile/ infected abscess Analgesia Collateral damage GB, pleura Infection Constipation

36 Sorafenib and impact The SHARP trial included only patients with preserved liver (Child-Pugh A). Data in Child-Pugh B are scarce.

37 SIRT and Liver Function Liver tissue protected Liver complication rate low N=78. No liver decompensation CPS A to B Except for complications- gastric bleeding? Post chemo radiosensitisation World Journal of Surgical Oncology 2011

38 Cost Effectiveness of sorafenib The incremental cost-effectiveness ratio was $US62 473/life-year gained. Cost: USD6696/ year Effect: Gain 1.05 LY Conclusions: Sorafenib is cost-effective compared to best supportive care, US society is willing to pay (i.e. $US $US ) ICER significantly lower than alternative thresholds suggested in recent years ($US $US /life-year gained, or $US /quality-adjusted life-year) in oncology Carr JGH 2010

39 Conclusion Liver Function is a key factor affecting HCC overall survival. Treatment must be tempered to the patient s liver function for tolerability and potential benefit Advanced liver disease- Childs C with severe PHT may not do well with treatment and survival may not be prolonged. Treatment may even hasten demise with further loss of normal liver tissue Understanding potential complications allows for targeted monitoring and early treatment to reduce morbidity and mortality.

40 Thank You