CL2017001088A1 - Regimen de dosificación para interferón pegilado - Google Patents

Regimen de dosificación para interferón pegilado

Info

Publication number
CL2017001088A1
CL2017001088A1 CL2017001088A CL2017001088A CL2017001088A1 CL 2017001088 A1 CL2017001088 A1 CL 2017001088A1 CL 2017001088 A CL2017001088 A CL 2017001088A CL 2017001088 A CL2017001088 A CL 2017001088A CL 2017001088 A1 CL2017001088 A1 CL 2017001088A1
Authority
CL
Chile
Prior art keywords
dosing regimen
pegylated interferon
pegiled
interferon
treatment
Prior art date
Application number
CL2017001088A
Other languages
English (en)
Inventor
Ko Chung Lin
Christoph Klade
Oleh Zagrijtschuk
Original Assignee
Pharmaessentia Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmaessentia Corp filed Critical Pharmaessentia Corp
Publication of CL2017001088A1 publication Critical patent/CL2017001088A1/es

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Communicable Diseases (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)

Abstract

<p>SE DESCRIBE UN INTERFERÓN TIPO I PEGILADO PARA USO EN EL TRATAMIENTO DE UNA ENFERMEDAD INFECCIOSA, CÁNCER O ENFERMEDAD MIELOPROLIFERATIVA EN UN SUJETO EN NECESIDAD DEL MISMO, EN DONDE UNA DOSIS DE 50 A 540 UG DEL INTERFERÓN TIPO I PEGILADO SE ADMINISTRA AL SUJETO A INTERVALOS REGULARES DURANTE UN PERIODO DE TRATAMIENTO, EL INTERVALO DE 3 A 8 SEMANAS.</p>
CL2017001088A 2014-11-06 2017-05-02 Regimen de dosificación para interferón pegilado CL2017001088A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP14192114 2014-11-06

Publications (1)

Publication Number Publication Date
CL2017001088A1 true CL2017001088A1 (es) 2018-01-12

Family

ID=51945707

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2017001088A CL2017001088A1 (es) 2014-11-06 2017-05-02 Regimen de dosificación para interferón pegilado

Country Status (32)

Country Link
US (3) US11559567B2 (es)
EP (2) EP3215193B1 (es)
JP (2) JP6820841B2 (es)
KR (2) KR102724837B1 (es)
CN (1) CN107530403A (es)
AU (1) AU2015342908B2 (es)
BR (1) BR112017009193A2 (es)
CA (1) CA2964390A1 (es)
CL (1) CL2017001088A1 (es)
DK (1) DK3215193T3 (es)
EA (1) EA037151B1 (es)
ES (1) ES2966888T3 (es)
FI (1) FI3215193T3 (es)
HK (1) HK1243627A1 (es)
HR (1) HRP20231732T1 (es)
HU (1) HUE064909T2 (es)
IL (1) IL251627B (es)
LT (1) LT3215193T (es)
MX (1) MX389844B (es)
MY (1) MY191506A (es)
NZ (1) NZ730924A (es)
PH (1) PH12017500617B1 (es)
PL (1) PL3215193T3 (es)
PT (1) PT3215193T (es)
RS (1) RS65015B1 (es)
SG (1) SG11201702798PA (es)
SI (1) SI3215193T1 (es)
SM (1) SMT202400028T1 (es)
TW (1) TWI737583B (es)
UA (1) UA122867C2 (es)
WO (1) WO2016073825A1 (es)
ZA (1) ZA201702704B (es)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190374611A1 (en) * 2017-01-18 2019-12-12 INSERM (Institut National de la Santé et de la Recherche Médicale) Methods and pharmaceutical compositions for the treatment patients suffering from myeloproliferative disorders
US11414698B2 (en) * 2018-03-22 2022-08-16 Chang Gung Medical Foundation Chang Gung Memorial Hospital At Chiayi Method of quantifying mutant allele burden of target gene
CN115968291A (zh) * 2020-04-22 2023-04-14 南湖制药公司 聚乙二醇化干扰素tau及其组合物和方法
AU2022221496A1 (en) * 2021-08-29 2023-03-16 Pharmaessentia Corporation Method of Using Pegylated Interferon-alpha

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5382657A (en) * 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
US5919455A (en) 1993-10-27 1999-07-06 Enzon, Inc. Non-antigenic branched polymer conjugates
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
US5951974A (en) 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
US5824784A (en) 1994-10-12 1998-10-20 Amgen Inc. N-terminally chemically modified protein compositions and methods
US5738846A (en) * 1994-11-10 1998-04-14 Enzon, Inc. Interferon polymer conjugates and process for preparing the same
US5932462A (en) 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
TW517067B (en) 1996-05-31 2003-01-11 Hoffmann La Roche Interferon conjugates
US6824768B2 (en) * 1998-12-18 2004-11-30 Schering Corporation Ribavirin-pegylated interferon alfa induction HCV combination therapy
MXPA02001296A (es) * 1999-08-13 2002-07-22 Hoffmann La Roche Micofenolato mofetil en asociacion con peg-ifn-alfa.
KR20020034181A (ko) 1999-08-27 2002-05-08 맥시겐 에이피에스 새로운 인터페론 베타-유사 분자
JP2003513681A (ja) 1999-11-12 2003-04-15 マキシゲン・ホールディングス・リミテッド インターフェロンガンマ・コンジュゲート
US7125843B2 (en) 2001-10-19 2006-10-24 Neose Technologies, Inc. Glycoconjugates including more than one peptide
OA13063A (en) 2001-11-20 2006-11-10 Pharmacia Corp Chemically-modified human growth hormone conjugates.
US20030171285A1 (en) 2001-11-20 2003-09-11 Finn Rory F. Chemically-modified human growth hormone conjugates
PT3025726T (pt) 2002-01-18 2020-01-09 Biogen Ma Inc Compostos do polímero polialquileno e utilizações dos mesmos
US7345150B2 (en) 2002-03-26 2008-03-18 Medical University Of Toledo Albumin-based colloid composition having at least one protected thiol region, methods of making, and methods of use
JP4764630B2 (ja) 2002-09-09 2011-09-07 ネクター セラピューティックス 水溶性ポリマーアルカナール
US7563810B2 (en) 2002-11-06 2009-07-21 Celgene Corporation Methods of using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione for the treatment and management of myeloproliferative diseases
RS20050501A (sr) 2002-12-26 2007-08-03 Mountain View Pharmaceuticals Inc., Polimerni konjugati citokina,hemokina,faktora rasta, polipeptidnih hormona i njihovih antagonista sa očuvanom aktivnošću vezivanja receptora
PT2644206T (pt) 2003-05-23 2019-07-10 Nektar Therapeutics Derivados de peg contendo duas cadeias de peg
NZ547168A (en) 2003-11-24 2010-05-28 Biogenerix Ag Glycopegylated erythropoietin
AU2005278903A1 (en) 2004-08-31 2006-03-09 Pharmacia & Upjohn Company Llc Glycerol branched polyethylene glycol human growth hormone conjugates, process for their preparation, and methods of use thereof
US7365127B2 (en) 2005-02-04 2008-04-29 Enzon Pharmaceuticals, Inc. Process for the preparation of polymer conjugates
EP1869079A2 (en) 2005-03-11 2007-12-26 Siegfried Ltd. Di-polymer protein conjugates and processes for their preparation
WO2006094530A1 (en) 2005-03-11 2006-09-14 Siegfried Ltd. Di-polymer protein conjugates and processes for their preparation
CN101002944B (zh) 2006-01-17 2012-07-25 中国科学院过程工程研究所 支链聚乙二醇-干扰素结合物及其制备方法
EP1834963A1 (en) 2006-03-13 2007-09-19 Siegfried Ltd. Di-polymer protein conjugates and processes for their preparation
CN101104078B (zh) 2006-07-11 2011-11-02 北京美倍他药物研究有限公司 多肽及蛋白药物的聚乙二醇偶合物
CN101108895B (zh) 2006-07-19 2011-10-26 北京键凯科技有限公司 聚乙二醇乙醛衍生物及其与药物的结合物
US20090035273A1 (en) * 2006-08-18 2009-02-05 Pepgen Corporation Combination treatment method with interferon-tau
CN1966547B (zh) 2006-11-06 2011-11-09 中国药科大学 双链结构的聚乙二醇衍生物的制备及其与药物分子的结合
CN1970572A (zh) 2006-12-21 2007-05-30 北京三元基因工程有限公司 干扰素α突变体及其聚乙二醇衍生物
CL2008002399A1 (es) 2007-08-16 2009-01-02 Pharmaessentia Corp Conjugado sustancialmente puro que posee una porcion polimerica, una porcion proteica (interferon alfa 2b) y un ligante alifatico de 1 a 10 atomos de carbono, util en el tratamiento de las hepatitis b o c.
CN101636414B (zh) * 2007-09-04 2012-02-15 厦门伯赛基因转录技术有限公司 聚乙二醇修饰的干扰素α2b及其制备方法和应用
KR101483814B1 (ko) 2007-09-04 2015-01-16 바이오스티드 진 익스프레션 테크. 컴파니 리미티드 폴리에틸렌 글리콜에 의해 변형된 인터페론 알파 2ａ, 이의 합성 방법 및 용도
CN101491682A (zh) 2008-04-30 2009-07-29 北京凯正生物工程发展有限责任公司 聚乙二醇化重组人干扰素ω偶合物及其制备工艺
JP5639585B2 (ja) 2008-07-31 2014-12-10 ファーマエッセンティア コーポレイション ペプチド−ポリマー共役体
CN101671390B (zh) 2008-09-10 2012-10-03 海南四环心脑血管药物研究院有限公司 人干扰素α衍生物及其聚乙二醇化修饰物的制备和用途
CN101514229B (zh) 2009-04-03 2012-05-09 海南四环心脑血管药物研究院有限公司 人干扰素α衍生物及其聚乙二醇化修饰物
UA109646C2 (uk) 2009-12-10 2015-09-25 Терапевтичне застосування кон'югатів білка з полімером
US20120310140A1 (en) * 2010-12-01 2012-12-06 Spinal Modulation, Inc. Directed delivery of agents to neural anatomy

Also Published As

Publication number Publication date
UA122867C2 (uk) 2021-01-13
EP4282485A2 (en) 2023-11-29
US20170326206A1 (en) 2017-11-16
JP6820841B2 (ja) 2021-01-27
CN107530403A (zh) 2018-01-02
PT3215193T (pt) 2023-12-15
KR20170083074A (ko) 2017-07-17
FI3215193T3 (fi) 2023-12-28
PH12017500617B1 (en) 2024-07-03
TWI737583B (zh) 2021-09-01
US12343381B2 (en) 2025-07-01
ES2966888T3 (es) 2024-04-24
MX389844B (es) 2025-03-04
EP3215193B1 (en) 2023-10-04
KR20230079520A (ko) 2023-06-07
ZA201702704B (en) 2020-10-28
EA201790991A1 (ru) 2017-11-30
HK1243627A1 (zh) 2018-07-20
US20250186552A1 (en) 2025-06-12
WO2016073825A1 (en) 2016-05-12
EP4282485A3 (en) 2024-01-17
NZ730924A (en) 2022-04-29
PL3215193T3 (pl) 2024-03-18
TW201618808A (zh) 2016-06-01
JP2017533192A (ja) 2017-11-09
US20230131552A1 (en) 2023-04-27
LT3215193T (lt) 2024-01-25
AU2015342908A1 (en) 2017-05-04
EP3215193A1 (en) 2017-09-13
DK3215193T3 (da) 2024-01-08
IL251627A0 (en) 2017-06-29
BR112017009193A2 (pt) 2018-01-30
KR102724837B1 (ko) 2024-10-31
MY191506A (en) 2022-06-28
AU2015342908B2 (en) 2021-06-24
EP3215193A4 (en) 2018-07-25
MX2017005244A (es) 2017-08-18
RS65015B1 (sr) 2024-01-31
EA037151B1 (ru) 2021-02-11
US11559567B2 (en) 2023-01-24
SG11201702798PA (en) 2017-05-30
CA2964390A1 (en) 2016-05-12
KR102540109B1 (ko) 2023-06-02
SI3215193T1 (sl) 2024-02-29
IL251627B (en) 2021-12-01
JP2021001184A (ja) 2021-01-07
PH12017500617A1 (en) 2017-09-04
SMT202400028T1 (it) 2024-03-13
HRP20231732T1 (hr) 2024-03-15
HUE064909T2 (hu) 2024-04-28

Similar Documents

Publication Publication Date Title
JOP20200192A1 (ar) أجسام مضادة لـ tigit
MX2022009352A (es) Sal de hemisulfato de nucleotido para el tratamiento del virus de hepatitis c.
MY172578A (en) Oral dosing of glp-1 compounds
EA201791256A1 (ru) Производные хиназолина, применяемые для лечения вич
SV2018005682A (es) Composiciones terapeuticas para el tratamiento del virus de inmunodeficiencia humana
MX2016016666A (es) Derivados de acido boronico y usos terapeuticos de los mismos.
MX2016015093A (es) Derivados de acido boronico y sus usos terapeuticos.
EA201690687A1 (ru) Ингибиторы репликации вируса иммунодефицита
UA115811C2 (uk) Стабільний розчин об&#39;єднаних баклофену, сорбіту і налтрексону для перорального застосування
CR20150314A (es) Pirimido-[4,5-b]-quinolina-4,5 (3h, 10h)-dionas como supresoras de mutación sin sentido
CU24493B1 (es) Complejo de torio dirigido a tejido
AR099558A1 (es) Régimen de dosaje del compuesto fgf-18
ECSP16096831A (es) Derivados de naftiridinadiona
CL2016002879A1 (es) Composiciones farmacéuticas para tratar enfermedades infecciosas
MX2021008738A (es) Regimenes de dosificacion de melflufen para cancer.
CY1121566T1 (el) Νευροπροστατευτικο και ενδειξη αυτου
MX2018005358A (es) Comprimido de dosis alta que contiene mesalazina optimizado.
EA201691860A1 (ru) Пептидный медикамент в виде сухого порошка
MX2017005244A (es) Regimen de dosificacion para interferon pegilado.
EA201500942A1 (ru) ПРОТИВОВИРУСНЫЙ ИНДОЛО[2,3-b]ХИНОКСАЛИН
CL2020000471A1 (es) Regímenes de tratamiento.
EA202091743A1 (ru) Вакцинация дендритными клетками параллельно с химиотерапией
MX369039B (es) Vacuna contra el circovirus porcino tipo 2.
RU2014115406A (ru) Применение 8-(трифторметил)бензо[f][1,2,3,4,5]пентатиепин-6-амина в качестве антидепрессанта
AR111017A1 (es) Sal hemisulfato de un compuesto nucleotídico para el tratamiento del virus de la hepatitis c