Clinical Case n. 3 Massimo Puoti AO Ospedale Niguarda Ca Granda Milano, Italy

Transcription

1 Clinical Case n. 3 Massimo Puoti AO Ospedale Niguarda Ca Granda Milano, Italy

2 Disclosures Member of advisory boards &/or speaker in own events &/or investigator in RCT &/or research grants &/or teacher during courses for employees for Janssen, Vertex, MSD, Roche, ViiV, GSK, Abbott, Abbvie, Novartis, BMS, Gilead Sciences, Boehringer Ingelheim, Astellas, Astra Zeneca.

3 Clinical Case presentation 1: Clinical History Male born on september 1961; non smoker; alcohol < 40 g/d until 1989 then abstinent; married with a 47 years old woman HCV-; 2 sons HCV-; BMI 26 Kg/m 2 Family history of HCV: mother died of HCV cirrhosis at 62yrs.; 1 brother died after LT for decompensated cirrhosis at 40 yrs 1989 Increased aminotrasferases HCVAb+ HCV G1b PLT /mL 1994 Liver biopsy A2F2 PLT /mL 1 st cycle of recombinant alpha interferon + RBV 1200 mg/d 1999 HCVRNA late negativization on qualitative assay (< 50 IU/mL) then relapse after treatment withdrawal 2 nd cycle 2001: leukocyte derived alpha interferon mg /d RBV + amantadine HCVRNA always positive (no data on quantitative HCVRNA during both treatment cycles). From 2001 to cycles of leukocyte derived interferon alfa duration 1-2 years PLT during treatment /mL with mild increase above baseline; between interferon courses progressive decrease of PLT count 2004 Fibroscan Stiffness 22.8 IQR 4.2 Succes rate 12%

4 Clinical case presentation 1: first visit 1 st visit: July 2011 HCVAb+ HCVRNA+ HCV Genotype 1b HBsAg- anti HBc- anti HBs+ (vaccinated) HAVAb IgG + PLT /mL GGT 54 IU/mL ALT 56 IU/mL AST 44 IU/mL ALP 89 IU/mL INR 1.1 Total Bilirubin 1 mg/dl Albumin 4.6 g/dl Creatinine, urinary stick, blood glucose, triglyceride, cholesterol, transferrin saturation, fibrinogen + alpha 1 antitripsyn in the normal range Anti-LKM, SMA and AMA negative; ANA positive 1/80 homogeneous pattern

5 Clinical case presentation. Question 1 Summary 50 years old man with chronic hepatitis C and family history of liver disease Fibroscan F4 relapser then non responder to suboptimal anti HCV treatment; ANA reactivity thrombocytopenia; no other comorbidities How to complete diagnostic workup? US & EGDS IL 28 rs SNP HOMA Vitamin D Review of 1994 histology Haematological consultation A new Fibroscan

6 Clinical case presentation 3 Review of 1994 histology: Chronic hepatitis C no alpha 1 antitripsin or fibrinogen or copper or iron storage no signs of autoimmune hepatitis IL 28 rs SNP CT HOMA 5.4 vitamin D normal US no focal lesion irregular margin splenomegaly Fibroscan Stiffnesss 23 KPa IQR 2,1 Success rate 72% EGDS F1 varices no red signs; no congestive gastropathy Haematological consultation: blood tests + BONE MARROW BIOPSY: Diagnosis: Immune Thrombocytopenia

7 Milan Italy July 2011 Clinical case presentation. Question 2 Telaprevir & Boceprevir still not available; Eltrombopag available and reimbursed for ITP only if PLT < EAP for Telaprevir & NPP for Boceprevir planned but still not finalized What to do? Treatment with PEGIFN + RBV off label (PLT < /mL) Watchful waiting

8 Clinical case presentation. Question 3 The patient was not treated and started follow up December 2011: 2 liver focal lesion segment IV diameter 2.2 cm and segment II 1,1 cm near gallbladder NMR : HCC Liver function and liver enzymes: stable Two nodules of HCC in a CTP A5 cirrhosis with MELD 7 and portal hypertension (Esophageal varices) ; RFTA or PEI not feasible What to do? TACE + listing for OLT Liver resection What about anti HCV Tx?

9 Clinical case presentation 4 Consultation with the transplant team: Liver resection then listing for OLT in case of relapse Anti HCV treatment if no HCC lesions at 3 mo. January 2012 laparoscopic Da Vinci robot assisted liver resection II & IV segment + cholecistectomy Histology: two nodules of 2 and 1 cm grade II HCC without microvascular invasion; micronodular cirrhosis with chronic hepatitis April 2012: NMR no HCC relapse. PLT /mL INR 1.1 Bilirubin 1 mg/dl. AST 76 ALT 90 GGT 65 normal creatinine Not eligible for Telaprevir EAP and Boceprevir NPP planned Eltrombopag then request for Telaprevir NPP

10 Clinical case presentation 5 Eltrombopag was started at 25 mg/d on may 29 th 2012 PLT > after 2 weeks Maintenance: Eltrombopag 25 mg 1-3 pills week Telaprevir NPP was requested Telaprevir (still not reimbursed by Italian NHS) Patient started: Telaprevir 750 mg thrice daily + Pegasys 180 mcg weekly + Ribavirin mg 600 bid on June 13th 2012

11 Clinical case presentation 6 Date 13/6 21/6 28/ 6 5/7 12/7 19/7 26/7 09/08 16/08 06/09 13/09 PLT N Hb ALT INR Total Bil Alb HCVRNA IU/mL Abbot HCVRNA IU/mL Roche Eltrombopag 25 mg <12 <LLD <12 <12 <12 <LLD <LLD <12 <LLD <LLD <LLD <LLD 1/w 1/w 1/w 3/w 3/w 3/w 2/w 2/w 2/w 2/w 3/w

12 Clinical case presentation 7 During treatment: Mild rash treated with antihistamine + topical steroids Anal discomfort treated with local lidocaine No flu like symptoms; no infections Optimal adherence to treatment On July NMR non HCC lesions On September 6 th 2012 stop Telaprevir

13 Clinical case presentation Question 4 Date 04/10 PLT 70 N 680 Hb 10.9 ALT 100 INR 1.14 Total Bil 1.4 Alb 4.19 HCVRNA Abbott <12 HCVRNA roche <LLD Eltrombopag 25 mg 2/w N < 750. NMR on October no HCC lesions What to do? Decrease PEGIFN from mg/w Add G-CSF Stop anti HCV Tx

14 Clinical case presentation 8 Date 04/10 19/10 02/11 30/11 13/12 PLT N Hb ALT INR Total Bil Alb HCVRNA Abbott IU/mL <12 <LLD <12 < HCVRNA Roche IU/mL <LLD <LLD 95 Eltrombopag 25 mg 2/w 2/w 2/w 2/w 3/w G-CSF IU 1/w 1/w 1/w 1/w

15 Clinical case Question 5 HCV cirrhosis recent resection for HCC On eltrombopag for ITP Late breakthrough HCVRNA (24 th week) after P+R+T 12 w + PR 12 w What to do: Stop P+R Continue P+R Continue P+R and add Boceprevir

16 janu Clinical case presentation 9 Date 04/10 19/10 02/11 30/11 13/12 09/01 PLT N Hb ALT INR Total Bil Alb HCVRNA Abbott <12 <LLD <12 < HCVRNA roche <LLD <LLD Eltrombopag 25 mg 2/w 2/w 2/w 2/w 3/w 3/w G-CSF IU 1/w 1/w 1/w 1/w 1/w January 2013 NMR no HCC relapse. P & R were withdrawn