HCV
Treatment of recurrent hepatitis C virus infection with pegylated interferon plus ribavirin.
Boceprevir/Telaprevir triple therapy in liver transplantation No use pre-transplant (CUPIC experience!) (limited use in patients listed for HCC with compensated HCV1 cirrhosis) Use post-transplant aggravated by: toxicity (anemia, sepsis), additive complexity in management significant drug-drug interactions Boc with calcineurin inhibitors Tel with cyclosporine/tacrolimus
Boceprevir/Telaprevir triple therapy post-transplantation US CRUSH; European LT group SVR 41,2% (US), 52% (Europe) discontinuation 23% (US), 40% (Europe) blood transfusion 49% (US), 35% (Europe)
AASLD 2013: Sofosbuvir nei trapianti N. pazienti (terapia) Caratteristiche Risposta Commenti Curry PRE OLT #213 61 pts (sof 400mg + Rb 1g-1.2g, fino a 48w) Child≤7 HCC entro Milano 1a 39%, 1b 34% IL28CC 22% 75% experienced 41 pazienti trapiantati 93% negativi a OLT SVR12 post OLT 64% 2 sosp precoce (ARF e polmonite)
AASLD 2013: Sofosbuvir nei trapianti N. pazienti (terapia) Caratteristiche Risposta Commenti Charlton POST OLT #LB.2 40 pts (sof 400 mg + Rb 400 mg-1.2g, fino a 24 w ) Child<7; MELD≤17 55%1a, 28%1b; 15% 3; 40% cirrotici F3 23% IL28CC 33% 88% experienced OLT-TX: 6mo-10y RVR4: 100% EOT: 100% SVR4: 77% (27/35) Non interazioni farmaci; 20% EPO; 28% < dose Rb x anemia; No rigetto; 2 sosp prec (polmonite; HCC progressione).
AASLD 2013: Sofosbuvir nei trapianti N. pazienti (terapia) Caratteristiche Risposta Commenti Forns POST OLT USO COMPAS #1084 44pts Gruppo1: 32pt (Sof+Rb) Gruppo 2: 12pt (Sof,Peg,Rb) Durata: ≤ 48 w Gruppo1: MELD medio 16 1a 28%; 1b 53% FCH 47% Gruppo2: MELD medio 13 1a 42%; 1b 25% FCH 33% Gruppo 1: SVR12: 60% Relapse12: 10% SVR12: 50% Relapse12: 25% 64% clin improved; 25% morti SAE: Gruppo 1: 1 ARF Gruppo 2: 1 trombosi venosa profonda, 1 HCC multifocali
Studio fase 2; ABT-450/R + ABT-267 + ABT333 + Ribavirina nel post-trapianto 34 trapiantati non-cirrotici con infezione HCV1 ricorrente, > 12 mesi post-trapianto RVR in 34/34 EOTR in 13/13 SVR4 in 12/13 astenia e cefalea, nessun rigetto, 5 trattati con EPO Kwo, 2014
HBV
Strategies to minimize cost (and maintain efficacy) in HBV prophylaxis HBIG followed by antivirals only antivirals only HBIG/antivirals followed by no prophylaxis
29 pts, all HBV-DNA – at transplant, HBIG and LAM for 1 month HBIG stop long-term antiviral: randomized trials Buti M, 2003 29 pts, all HBV-DNA – at transplant, HBIG and LAM for 1 month randomized 15 HBIG + LAM 14 LAM 18 months median follow-up 3 (20%) HBV-DNA + 1 (7%)
HBIG stop long-term antiviral: randomized trials Buti M, 2007 6 patients on HBIG + LAM from previous study crossed over to LAM monoprophylaxis HBIG + LAM 9 LAM 20 83 months mean follow-up 1 (11%) HBsAg + 3 (15%)
HBIG stop long-term antivirals: randomized trials Angus PW, 2008 34 pts, median 4.5 y post-surgery 77% HBV-DNA – at transplant HBIG and LAM 18 HBIG + LAM 16 ADV + LAM 21 months median follow-up 0 HBsAg + 1 (6%)
HBIG stop long-term antiviral: randomized trials Teperman LW, 2013 37 pts, median 3.4 y post-surgery 52% HBV-DNA – , 70% HBeAg – at transplant HBIG with TENOFOVIR / EMTRICITABINE (TVD) for 24 wks: randomized TVD 18 HBIG and TVD 19 All HBsAg – at 72 weeks
No HBIG – Antiviral only Fung J, 2011 80 pts At transplant: 26% HBV-DNA – ; 74% HBV-DNA + , median log 3.5 cps/ml (1.5 – 8.8) ENTECAVIR (0.5 – 1 mg) After 26 m follow-up 91% cumulative loss of HBsAg 98% undetectable HBV-DNA reappearance of HBsAg in 10 pts after seroclearance no Entecavir resistance mutations no HBV related clinical event
No HBIG – Antiviral only Wadhawan M, 2013 75 pts, HBV-DNA 2000 IU/ml at LT Prophylaxis: 19 LAM and ADV 42 ETV 12 TDF 2 TDF and ETV After a median follow-up of 21 months (1-83) all patiens HBV-DNA – 66 pts cleared HBsAg, 19 seroconversion to anti-HBs 9 pts remained HBsAg + RECURRENCE RATE = 8%
Role of quantitative HBsAg levels? Fung J, 2011 Pre-transplant HBsAg titers higher in pts with persistent/recurrent HBsAg (median 868.95 IU/ml) compared with HBsAg negative post-transplant (415,10 IU/ml) (p = 0,31) HBV-DNA loss not associated with HBsAg loss; Low HBV-DNA (< 5 log copies/ml) with low HBsAg level (< 3 log IU/ml): cumulative rate of HBsAg seroconversion = 100% at 18 m
HDV
Results 3 HDV/HBV rate Overall Number: 433/2,260 HBsAg+ (19%) overall and 45/128 (35%) in 2011 Total LTs: 433/10,365 ( 4%) overall and 45/698 (6.4%) in 2011 Overall 20 20 20 20
Results 4 Indication to LT: CirrhosisAcuteHCC Cirrhosis Cirrhosis Indication to LT in HBV (HDV neg) patients in the last 5 years Indication to LT in HDV patients in the last 5 years Cirrhosis mean 63% Cirrhosis mean 45% 21 21 21 21