Clinica patologie del fegato 20142015 Clinical Activity

Basovizza 19 novembre 2015

Clinical Activity and research

Diagnosis and treatment

Hypobetalipoproteinaemia and steatosis

NAFLD – NASH (metabolic syndrome)

Acute and chronic AFLD

HBV +/- HDV

HCV – direct antiviral treatment

Primary biliary Cirrhosis, Primary Sclerosing Cholangitis

Autoimmune hepatitis

Decompensated Cirrhosis

Hepatocellular carcinoma (HCC)

Cirrhotic patients surveillance

Loco-regional treatment in DH regimen

Outpatient activity

First visit and control (three outpatient units from Monday to Friday)

Day Hospital Activity. More frequent procedures in DH:

Liver biopsies

Blood and derivatives transfusions in liver disease patients

Martial treatment

Paracentesis

Acute hepatic encephalopathy

Diagnostic angiography

Orthotopic Liver Transplant's Staging (OLT)

Focal Liver Lesion treatment (CEAT, thermoablation)

Cysts drainage / Alcoholization

After variceal ligature monitoring

Share wave elastography: a non invasive instrument for Chronic Liver Disease staging, standardized in HCV

Clinical Activity

CPF TOT 2014 ott-15

PRESTAZ

CONT 3803 2893

1 VIS 526 428

PREL 2329 1640

SAL/INF/PARAC/INIEZ/MEDIC630 157

elasto 354 380

TOT PREST. 7642 5498

Tutoring CPF 2014

Medical school degree Tutoring

Specialisation in Internal Medicine tutoring

Nursing science degree tutoring

Specialisation in Gastroenterology (2014)

Terminated clinical studies:

BR129

Prophesys

Gideon

Astro (stopped for recruitments problems)

STEP

HCC NASH EASL

Dionysos 1-2

Por Fesr (HCC)

Clinical studies 2010-2014

Ongoing clinical studies:

PBC (Invernizzi)

NECTE (HCC)

FRA 2014 Staminal cell

FRA Bariatric

Silimet (coordination)

Projects

CPF coordination in RER (Regional liver network )

AIFA drug control for DAA

Alcohol

Clinical studies 2015

SILIMET e NAFLD

Background and motivations of the study

The frequency of steatosis in general population is about 35-40 %

Increasing NAFLD prevalence in Italy and occidental world secondary to diabetes and obesity

It seems that NAFLD will become the most frequent liver disease cause in the next decades

Second aetiology for liver transplantation in USA

NAFLD as marker for cardiovascular disease, diabetes or metabolic syndrome. It also can lead to more sever liver disease, steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)

At now not sure drugs or nutraceutical are available for NAFLD or NASH treatment, even if there are a lot of molecules in experimentation

Characteristics of the study

Multicentric (60 Italian centers)

Controlled

Randomized by center

The major criteria for entering the study is the presence of steatosic ultrasound pattern in the liver

The aim of the study is to assess efficacy and safety of Legalon E in association with diet regimen and movement in a 6 month treatment in patients with NAFLD

The study is controlled with a group of patients treated with diet regimen and movement only

The primary objective of the study is to assess the responder frequency (measured by HIS reduction of at least 2 points) in sperimental groups

The secondary objective are assessment of the difference between the two groups in term of:

FLI (Fatty Liver Index)

LAP (Lipid Accumulation Product)

AST/ALT

Insulin resistance by HOMA reduction

In SF-12 score questionary reduction

Safety and tolerability

Steatosys improvement

Multicentric, randomized and controlled clinical trial, on efficacy and safety of use of a nutraceutical (Legalon E) associated with dietary and behavioral norms in patients

with nonalcoholic fatty liver disease (NAFLD)

Males and females > 18 anni e < 75 years of age

Alcohol consumption < 30 gr/die

Informed consent module signed

US, done in the last 3 months,with ultrasound pattern of steatosys (NAFLD, in the absence of cirrhosis evidence)

ALT or AST > 40UI/L or AST/ALT < 1 during screening period

Weist circonference >94 cm (males) or 80 cm (females)

Glicemia > 5.6 mmol/L (100 mg/dl)

Triglyceridemia > 1.7 mmol/L (150 mg/dl)

No changes in anti diabetic treatment (if applicable) between screening and treatment

Inclusion criteria

Alcohol consumption > 30 gr/day

Use of silimarine or other preparation containing marian in the 30 days before the screening

Other antiossidant product as vitamin E, vitamin C, glutathione in the 30 days before the screening

use of pentossifillina o gemfibrozil entro i 30 giorni precedenti lo screening

Allergy or o intollerance to silimarine or Marian card extract

BMI ≥40

Pregnancy or Brest feeding

Clinical evidence of actual chronic or active hepatitis

Esclusion criteria

Each centre will use his own randomisation list on which the patient will be randomised in

Group A: diet and exercise

Group B: to these patients, in addition to the requirements for group A, it will be directed even daily intake, for 6 months, of 2 tablets of Legalon E

Every collaborator received login e password for e-crf

Group of 10 consecutive patients that fits inclusion and exclusion criteria will be randomised

When the e-crf will be completed the system will assign the patient to the treatment or diet exercise only

Randomization

SILIMET e NAFLD

CPF: 14 patients enrolled

New direct antiviral drugs for HCV positive chronic

liver disease (DAA)

Proteasis and polimerasis inhibitors

…the past

87-99 % SVR 12

…the present

New direct antiviral drugs for chronic HCV positive (DAA):

efficacy

Terapia del paziente con cirrosi in classe di Child-Pugh A o B e/o con HCC con risposta completa a terapie resettive chirurgiche o loco-regionali, non candidabili a trapianto epatico, nei quali la malattia epatica sia determinante per la

prognosi

SCHEMI TERAPEUTICI Genotipo 1a, 1b Child

Pugh A

Genotipo 1 a, 1b Child

Pugh B Genotipo 2 Genotipo 3 Genotipo 4 Child Pugh A Genotipo 4 Child Pugh B

Costo 12 settimane di

terapia*

PegIFN + RBV + SMV 48 settimane (SMV 12

settimane) sconsigliato sconsigliato € 15.000

PegIFN + RBV + SMV 24/48 settimane (SMV 12

settimane) sconsigliato € 15.000

PegIFN + RBV + SMV 48 settimane (SMV 12

settimane) sconsigliato € 15.000

PegIFN + RBV + DCV 12/24 settimane sconsigliato sconsigliato € 17.000

PAR/OMB/RTV + RBV 24 settimane ottimale subottimale € 24.840

PAR/OMB/RTV + DAS + RBV 12-24 settimane ottimale subottimale € 27.000

PegIFN + RBV + SOF 12 settimane sconsigliato sconsigliato subottimale sconsigliato sconsigliato € 37.000

SOF + RBV 24 settimane sconsigliato sconsigliato subottimale subottimale sconsigliato € 37.000

SOF + RBV 12/16 settimane ottimale € 37.000

SOF + LDV + RBV 12 settimane ottimale ottimale ottimale ottimale € 40.700

SOF + LDV 24 settimane ottimale ottimale ottimale ottimale € 40.700

SOF + LDV + RBV 24 settimane subottimale € 40.700

SOF + SMV + RBV 12 settimane ottimale subottimale ottimale subottimale € 52.000

SOF + DCV + RBV 12 settimane ottimale ottimale ottimale ottimale € 54.000

SOF + DCV 24 settimane ottimale ottimale ottimale ottimale € 54.000

SOF + DCV ± RBV 24 settimane ottimale € 54.000

* i costi sopra indicati sono al lordo di eventuali scontri riconosciuti al SSR secondo accordi negoziali in considerazione del fatto che tali accordi al momento non sono noti o lo sono solo parzialmente. Sono inoltre esclusi i costi relativi a PEG-IFN e RBV.

Il costo finale per trattamento è il medesimo a prescindere dalla durata della terapia, che può essere di 12, 24, 48 settimane (flat rate). , ma quello da sostenere al momento dell’ acquisto del farmaco è proporzionale alla durata della terapia ( 24 settimane doppio di 12

settimane . Sono i costi effettivi che intanto pesano sui bilanci aziendali sintanto le procedure di pay back non saranno terminate con successo. (€ 54.000 finali sono € 108.000 intanto da mettere in bilancio). [NOTA PER I REVISORI: VALUTARE CONGIUNTAMENTE SE TENERE I

DATI CON FLAT RATE]

DAA prescribing centre in FVG (Hub)

Udine (Clinica medica, Malattie infettive)

Pordenone (divisione di Medicina)

Trieste (CLINICA PATOLOGIE DEL FEGATO, Malattie infettive)

Clinica patologie del fegato's activity DAA for HCV

50 patients in treatment with DAA

1 February-19 November 2015

Problems

Lack of FVG register for HCV positive patients reporting CLD staging (as in Veneto or other regions)

Restrictive AIFA criteria

Impact of press agency and patients associations

Not clear timing of price reduction for new DAA

Prescribing centre cooperation

n. patients/ class age

Genotype < 18 18-50 51-65 >65 Total FVG

1 2 374 529 479 1384

2 3 123 131 280 537

3 2 220 135 55 412

4 0 54 44 7 105

5 0 3 1 0 4

6 0 0 0 0 0

Not performed 0 102 93 299 494

TOTALE 7 876 933 1120 2936

Viremic patients HCV + in FVG: regional 2014 report

Sex and class age distribution

New DAA FVG 2015

Monthly report

Coordination of RER

Second opinion

AIFA drug control for DAA

Multiregional project sponsored by AIFA (80.000 euros)

Regions: Fvg and Liguria

Cohordinator: Liguria (HIV-HCV)

Data base of HCV patients treated (2015-2016): clinical and drug control peculiarity

Fellowship

Future perspectives

Developement of a personalizzed treatment strategy

More attention in patient education in particular for metabolic diseases

Prognostic algoritms development for major CLD in particular HCC

Treatment of decompensate liver cirrhosis

Biobank organisation

Database riorganisation (Elastography, HCV, HBV, HCC) for best clinical and research operativity

Clinical staff Cristiana Abazia permanent staff medical doctor Antonella Copez Administrative operator Caterina Cecchi secretary Medical department

Saveria Lory Crocè Responsable

Valentina Lanzilotti Specialist in formation (c/o Med Clin) Daniele Macor Specialist in formation (Gastroent) Flora Masutti permanent staff medical doctor Daniela Mattiazzi Nurse Loredana Sumas Nurse

Milva Pagotto Nurse

Riccardo Patti Specialist in formation (c/o Clin Med )

Patrizia Piriavic Nurse

Claudio Tiribelli Director

Cinzia Ursic OSS

Paola Concas OSS

Cester Giulia Medical doctor

Thank you!