Challenges in the treatment of hepatitis C: Current state and - PowerPoint PPT Presentation

Challenges in the treatment of hepatitis C: Current state and activities of the German Center for Infection Research (DZIF) Thomas von Hahn Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover

Viral hepatitis continues to pose a public health challenge… Global annual mortality from hepatitis, HIV, tuberculosis and malaria, 2000-2015 WHO Global Hepatitis Report 2017

… but are there still challenges in treating HCV in individual patients? • Genotype 3 ? • Pre-treated • After liver transplant • Renal failure • Compensated and decompensated cirrhosis • HIV coinfection

A Case Challenges History HCV Genotype 3 • 44 y.o. male • • Presents to ER with hematemesis • ART plus Anti-HCV • RF: (Past?) IVDU and Alcohol Use • Risik of re-infection in IVDU Diagnoses Variceal bleeding • • Liver transplant: • Cirrhosis − HIV • HCV Genotype 3 Infection − Possible ALD component • HIV Infection under ART − „TX first“ or „Anti-HCV first“

Genotype 3

Genotype 3 Data from the GErman hepatitis C COhort (GECCO) Christensen et al. AASLD 2017 Abstract #63.

Current Recommendations for HCV Genotype 3 Treatment-naive Keine Zirrhose Kompensierte Zirrhose Recommended • Glecaprevir/Pibrentasvir • Glecaprevir/Pibrentasvir (8W) (12W) Sofosbuvir/Velpatasvir Sofosbuvir/Velpatasvir • • (12W) (12W) NS5A-experienced Keine Zirrhose Kompensierte Zirrhose Recommended • Sofosbuvir/Velpatasvir • Sofosbuvir/Velpatasvir /Voxilaprevir (12W) /Voxilaprevir + Ribavirin (12W) AASLD/IDSA Empfehlung 2017

Bourlière et al. NEJM 2017

HCV/HIV Co-Infection

Grazoprevir/Elbasvir in HCV Mono- and HCV/HIV Co-Infection C-WORTHY Trial. Sulkowski et al. Lancet 2015.

Risk of drug- drug interactions in HCV in real-life Anti-HCV Regime Höner zu Siederdissen et al. Clin Infect Dis. 2016

DDI between anti- HCV combinations and ART AASLD/IDSA Empfehlung 2017

Liver Transplantation

DZIF Cohort: DAA following liver TX (MHH/UKE) Ciesek et al. Transpl. Infect Dis 2016. (LDV/SOF/RBV)

Studies on HCV DAA treatment following liver TX All Studies Total: Patients 545 SAE‘s 99 Deaths 12 SVR DZIF Sites: • Hamburg • Hannover (1) Charlton et al. Gastro 2015 (LDV/SOF/RBV) (2) Manns et al. Lancet ID 2016 (LDV/SOF/RBV) (3) Poordad et al. Hepatol 2016 (DAC/SOF) (4) Ciesek et al. Transpl. Infect Dis 2016. (LDV/SOF/RBV) (5) Kwo et al. NEJM 2014. (DAS/OMB/PAR/RBV)

Advanced Cirrhosis

SOLAR-2 Studie: LED/SOF in Advanced Liver Disease  Pre-TX / Child C Subgroup: • SVR 81% Mortality 12% • Manns et al. Transpl. Lancet ID 2016.

DZIF analysis of management strategies in advanced HCV cirrhosis Independent variable Population • Strategies „TX before DAA“ vs. „DAA • Retrospective multicenter analysis before TX“ • Centers: Frankfurt, Hamburg, Hannover, Heidelberg, Tübingen Primary endpoint • Survival Inclusion criteria • Chronic Hepatitis C Secondary endpoints • Advanced Cirrhosis (MELD 15+) Liver function • • HCV status Exclusion criteria • TX status • Contraindication to liver TX • HCC

DZIF analysis of management strategies in advanced HCV cirrhosis Table 1. Baseline Characteristics total cohort DAA pre Tx no DAA pre Tx total 19 13 6 Age (years), mean ± SD 51,95 (±7,4) 52,15 (±7,03) 51,5 (±8,2) male gender, N (%) 15 (78,9) 9 (69,2) 6 (100) BMI (m/kg2), mean ± SD 28,55 (±5,4) 29,41 (±5,98) 26,7 (±3,0) INR, mean ± SD 1,57 (±0,25) 1,56 (±0,21) 1,59 (±0,31) Bilirubin (µmol/L), mean ± SD 78 (±58,3) 65 (±23,5) 104 (±92,2) Creatinine (µmol/L), mean ± SD 119 (±123,6) 92 (±84,7) 179 (±166,3) labMELD, mean ± SD 18,7 (±3,7) 17,5 (±1,7) 21,5 (±5,2) Child-Pugh score, mean ± SD 9,8 (±2,1) 9,2 (±1,99) 10,8 (±1,8) 13 6 Sandmann et al. Unpublished data.

DZIF analysis of management strategies in advanced HCV cirrhosis DAA pre TX No DAA pre TX Sandmann et al. Unpublished data.

What is the current key challenge in HCV? Glo lobal al Eradic ication ion by 2030 2030 ? ?

What is the current key challenge in HCV? Resistance testing Reinfections Vaccine ? Access to Care • HCV Genotype Subgenotype • • Chimäric Genotypes • Ledipasvir/Sofosbuvir • Sofosbuvir/Velpatasvir +/- • Acute vs. Chronic Infection Voxilaprevir Pretreatment • • Paritaprevir/Ombitasvir/Ritonavir • Resistance +/- Dasabuvir • Fibrosis • Glecaprevir/Pibrentasvir • Cirrhosis • Elbasvir/Grazoprevir • Co-Infections • Co-Morbidities Interferon ? Ribavirin ? • Co-Medications Liver TX ? New DAA‘s ?

Summary • Individual management can be challenging in 2018: – Very advanced cirrhosis (MELD 15+) – Combinations of unfavorable factors • Even in „challenging“ patient subgroups „per protocol“ SVR rates are very high – the challenge often lies in adverse events during therapy and thus „intention to treat“ SVR. • Key challenge is optimal individualized treatment in face of – Many available combinations – Many factors impacting optimal choice of regimen – High cost – Risk of resistance development