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Hepatitis C Unggul Budihusodo Departemen Ilmu Penyakit Dalam FKUI – RSCM.

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Presentasi berjudul: "Hepatitis C Unggul Budihusodo Departemen Ilmu Penyakit Dalam FKUI – RSCM."— Transcript presentasi:

1 Hepatitis C Unggul Budihusodo Departemen Ilmu Penyakit Dalam FKUI – RSCM

2 WORLD HEPATITIS DAY 28 JULY

3 Hepatitis C Radang (inflamasi) hati akibat infeksi virus hepatitis C (HCV) Radang (inflamasi) hati akibat infeksi virus hepatitis C (HCV) Ditularkan melalui darah dan/atau cairan tubuh yang terinfeksi (transfusi darah, hubungan seks, tato, tindik dan injeksi) Ditularkan melalui darah dan/atau cairan tubuh yang terinfeksi (transfusi darah, hubungan seks, tato, tindik dan injeksi) 80-90% kasus menunjukkan gejala dan tanda yang minimal, kecuali bila komplikasi telah terjadi (pada tahap lanjut)  “silent killer” 80-90% kasus menunjukkan gejala dan tanda yang minimal, kecuali bila komplikasi telah terjadi (pada tahap lanjut)  “silent killer”

4 WHO Wkly Epidemiol Rec 2000;75: Infeksi HCV: Masalah Global ! ( Di Dunia: 170 juta orang terinfeksi HCV ) Di Indonesia: ± 4 juta orang Di AS: ± 4 juta orang

5 Country Prevalence in general population Prevalence in dialysis population* referenc e (year) Netherlands0.1%3%1998 Italy0.5%22.5%1999 Belgium0.9%9.4%1998 Bulgaria1.1%65.8%1998 France1.1%16.3%2000 Turkey1.5%31.4%1998 USA1.8%10%2003 Saudi Arabia 1.8%57%2001 Moldavia4.9%75%1999 Egypt18.1%80%2000 Fabrizi F et al. Hepatology 2002 PREVALENCE OF HCV INFECTION *Infection of dialysis patients via nosocomial transmission

6 1a, 1b 2a, 2b, 3a 1a, 1b 2a, 2b, 2c, 3a 4 5a 1b 1b, 6 1b, 3a 3b 4 Fang JWS et al. Clin Liver Dis. 1997;1: Infeksi HCV: Masalah Global 1a, 1b, 2b, 3a 2a Indonesia: 1a+1b: 60 – 65% 2a: 17 – 26% Distribusi Geografis Genotipe HCV:

7 Penyakit sistemik bukan hanya hati yang menanggung!

8 (Sulaiman A, Selayang pandang Hepatitis C, 2004) INFEKSI HCV GLOBAL: Fenomena Gunung Es!  170 juta orang telah terinfeksi (di Indonesia 4 juta)  kasus baru/tahun  4,1% dari seluruh kasus karsinoma  meninggal/tahun < 10% simtomatik > 90% asimtomatik Didiagnosis menderita Hepatitis C Diobati Tidak terdiagnosis 8

9 Hepatitis C Kronik: Besaran Masalah di Indonesia  1-2% 1,2 (sekitar 3,4 juta) populasi Indonesia terinfeksi kronis oleh virus hep C (HCV)  60-65% (sekitar 2 juta) terinfeksi virus genotipe 1 (sulit diterapi)  20-25% (sekitar 474,000) akan mengalami sirosis dalam tahun  1-4% (sekitar 14,000) tiap tahun dari pasien sirosis akan menderita kanker hati dan 20%nya akan meninggal akjbat kanker hati dan gagal hati 1.Hepatitis C National Surveillance data 2009) 2.Study of chronic hepatitis C prevalence in health care professionals, 2008

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11 Infeksi Virus Hepatitis C (HCV) “Rumus 20” Infeksi Virus Hepatitis C (HCV) “Rumus 20” Pada infeksi HCV hanya 20% yang tidak berlanjut menjadi infeksi kronis Dalam waktu 20 tahun, 20% dari pasien hepatitis C berlanjut menjadi sirosis hati Sekitar 20% pasien sirosis akibat HCV akan meninggal karena kanker hati atau gagal hati

12 HCV HEPATITIS C KRONIK SIROSIS LANJUT KANKER HATI (20−30 tahun) Advanced LC* HCC* Normal CH/LC* Hepatitis C Kronik: Komplikasi Progresi penyakit hati *: CH = Chronic Hepatitis; LC = Liver Cirrosis; HCC = Hepatocellular Carcinoma

13 Risk factors for HCV infection Injecting drug users Blood transfusions before screening was introduced (in most countries before 1992) Needle stick injuries (healthcare workers) Haemodialysis and organ transplant patients Medical or dental interventions where equipment is not adequately sterilised Tattooing, body piercing, and shaving using unsterilised equipment Unprotected sex involving injury (even minor)

14 tindiknarkotika transfusi Hubungan seks berisiko suntikan tattoo 14

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16 Diagnosis Hepatitis C Bila termasuk Kelompok Risiko Tinggi atau pernah Bila termasuk Kelompok Risiko Tinggi atau pernah terpapar darah yang diduga terkontaminasi HCV: terpapar darah yang diduga terkontaminasi HCV: Pemeriksaan darah awal: SKRINING anti-HCV Pemeriksaan darah awal: SKRINING anti-HCV Pemeriksaan lanjutan bila anti-HCV positif: Pemeriksaan lanjutan bila anti-HCV positif: HCV RNA kuantitatif & genotipe HCV HCV RNA kuantitatif & genotipe HCV

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18 Skrining MenilaiPrediksi Lama respon “Sustained Penilaian Skrining Konfirmasi Terapi terapi Response” SGPT/SGOTX Anti-HCV by EnzymeX immunoassay (EIA) Supplemental assay X (RIBA*) for anti-HCV HCV RNA qualitativeXX assay HCV RNA quantitativeXX assay HCV genotypeX NIDDK. Chronic hepatitis C: current disease management. Kegunaan Uji Diagnostik *Tidak lazim dipakai lagi

19 Kriteria Diagnostik Infeksi HCV: Hepatitis C Akut Hepatitis C Akut 1. Diketahui paparan < 6 bulan* 1. Diketahui paparan < 6 bulan* 2. Anti-HCV positif / negatif 2. Anti-HCV positif / negatif 3. HCV RNA positif 3. HCV RNA positif 4. SGPT meningkat 4. SGPT meningkat * Operasi / transfusi / trauma dll. * Operasi / transfusi / trauma dll. Hepatitis C Kronik 1. Anti-HCV positif > 6 bulan 2. HCV RNA positif 3. SGPT meningkat / normal  Gejala & tanda biasanya ringan, tidak khas atau asimtomatik  Singkirkan penyebab lain (virus, obat, autoimunitas)  Pikirkan kemungkinan infeksi ganda (dgn HAV/HBV/HIV)  Periksa genotipe HCV  lama pemberian terapi IFN

20 Tests of liver condition Noninvasive tests of fibrosis and activity Noninvasive tests of fibrosis and activity Panel of biochemical markers, e.g. FibroTest Panel of biochemical markers, e.g. FibroTest Ultrasonography, FibroScan Ultrasonography, FibroScan Liver biopsy Liver biopsy Gold standard for grading inflammation and disease stage Gold standard for grading inflammation and disease stage

21 Tujuan Terapi Hepatitis C Tujuan primer = “sembuh” o Virus “lenyap” 1 o Stop perkembangan penyakit o Hilangkan gejala Tujuan Sekunder oCegah fibrosis 1 oCegah terjadinya sirosis 2 oCegah Gagal Hati oCegah Kanker Hati 2 1.Worman HJ. Hepatitis C: current treatment. 2. Peters MG et al. Medscape HIV/AIDS eJournal. 2002;8(1). Kriteria kesembuhan dalam praktek  bila tercapai SVR (Sustained Virological Response)

22 Sustained Virological Response (SVR) o SVR adalah tujuan utama terapi Hepatitis C o SVR = Jumlah virus dibawah batas deteksi (50 IU/mL) hingga 6 bulan setelah terapi selesai o Indikator terbaik untuk : Menilai perbaikan klinis (parameter kesembuhan) Menilai perbaikan klinis (parameter kesembuhan) Perbaikan histologis (regresi fibrosis) Perbaikan histologis (regresi fibrosis) Mencegah KHS Mencegah KHS

23 Genotipe virus Genotipe virus Jumlah virus dalam tubuh Jumlah virus dalam tubuh Usia & Gender pasien Usia & Gender pasien BMI (IMT) pasien BMI (IMT) pasien Kondisi penyakit hati Kondisi penyakit hati Kapan terapi dimulai Kapan terapi dimulai Ketaatan menjalani program terapi Ketaatan menjalani program terapi Faktor-faktor yang Memengaruhi Keberhasilan Terapi

24 Rekomendasi Terapi Hepatitis C kronik Perhimpunan Peneliti Hati Indonesia (PPHI) Baku emas terapi saat ini: Baku emas terapi saat ini: Kombinasi pegylated interferon alfa dan ribavirin Kombinasi pegylated interferon alfa dan ribavirin Pegylated interferon alfa: keunggulan farmakokinetik dan farmakodinamik vs. interferon alfa konvensional: Pegylated interferon alfa: keunggulan farmakokinetik dan farmakodinamik vs. interferon alfa konvensional: - 1 x seminggu - 1 x seminggu - efek supresi virus yang optimal - efek supresi virus yang optimal - efikasi lebih tinggi - efikasi lebih tinggi  Pegylated interferon ditoleransi lebih baik Durasi terapi tergantung pada genotipe HCV: Durasi terapi tergantung pada genotipe HCV: - Genotipe 1 / 4 : 48 minggu - Genotipe 1 / 4 : 48 minggu - Genotipe 2 / 3 : 24 minggu - Genotipe 2 / 3 : 24 minggu

25 Terapi Hepatitis C Kronik : Perkembangan Selama >10 tahun % Sustained vriologic response PEG-IFN + Ribavirin 48 weeks 54-63% IFN + Ribavirin 48 weeks 42% PEG-IFN 48 weeks 25-39% IFN 24 weeks IFN 48 weeks 6% 16%

26 100% 0% 1st dose 14–28 Days HCV RNA Maintenance phase Detection limit Interferon inhibits the virus AND enhances the immune response Inhibition of viral replication Immune system elimination of infected cells ? Induction phase Ferenci P, et al. Viral Hep Rev 1999; 5: 229 Lymphocyte

27 Side effects of treatment Experience of side effects varies between individuals Experience of side effects varies between individuals Side effects are reversible and appear to be dose dependent Side effects are reversible and appear to be dose dependent Side effects can be managed Side effects can be managed Dose reduction is a common management strategy Dose reduction is a common management strategy Referral to the multidisciplinary team as necessary Referral to the multidisciplinary team as necessary Psychiatrist or psychologist or counsellor Psychiatrist or psychologist or counsellor Dietician Dietician Social worker Social worker

28 Most common side effects of interferon treatment Flu-like symptoms Flu-like symptoms Fever, chills Fever, chills Headache Headache Fatigue or asthenia Fatigue or asthenia Myalgia, arthralgia Myalgia, arthralgia Cough Cough Nausea Nausea Anorexia Anorexia Diarrhoea Diarrhoea Pruritus Pruritus Rash Weight loss Psychiatric symptoms Depression Insomnia Alopecia Injection-site reaction Leukopenia Thyroiditis Autoimmunity Thrombocytopenia

29 Most common side effects of ribavirin treatment Haemolytic anaemia Haemolytic anaemia Teratogenicity Teratogenicity Cough and dyspnoea Cough and dyspnoea Rash and pruritus Rash and pruritus Insomnia Insomnia Anorexia Anorexia 1. REBETOL ®. PDR ® 2. Chutaputti A. J Gastroenterol Hepatol 2000; 15(suppl): E156

30 Beda antara PEGASYS dengan PEG-IFN α-2b Pegylated interferon alfa-2b (12KD) PEGASYS ® (40KD) Interferon Interferon alfa-2b Interferon alfa-2a Struktur PEG Kecil, linier, 12KD PEG Besar, bercabang, 40KD PEG Isomer posisional 146 Ikatan protein Ikatan uretan tidak stabil Ikatan amida stabil 1. Bailon P, et al. Bioconjugate Chem 2001; 12: Kozlowski A, et al. BioDrugs 2001; 15: Wang Y-S, et al. Biochemistry 2000; 39: Youngster S, et al. Curr Pharm Des 2002; 8: Grace M, et al. J Interferon Cytokine Res 2001; 21: 1103

31 PEGASYS ® (Peginterferon Alfa-2a [40KD]) tidak perlu disesuaikan dengan berat badan Volume distribusi PEG-IFN a-2a (40KD) kecil 180  g Lamb MW, Martin NE. Ann Pharmacother. 2002;36:

32 Original Article: HEPAT ITIS C VIRUS INFECTION IN PATIENTS ON LONG TERM HEMODIALYSIS Abdul Karim Zarkoon*, Khalid Shah**, Habib ur Rehman***, Aamir Daud****, Jamil Ahmed*****  January 2006 to June 2007  23/97 (23.7%) were anti-HCV positive  history of dialysis for more than two years is a significant risk factor for getting HCV infection  HDU in others: Lahore 68%; India 83%; Tunisia 33%; Saudi Arabia 46%; Swiss 5%; USA 10%; Egypt 80% (Gomal Journal of Medical Sciences 2008, Vol. 6, No. 1)

33 Prevention and Control of Viral Hepatitis in Spain: Strict adherence to the universal infection control precautions. Pachon I, Shouval D. Viral Hepatitis 2007; 15 (1)

34 PEG Attachment Versus Detachment Absorption BLOOD Rapid degradation by peptidases PEGASYS ® (40KD) (Stable Bond)Small linear PEG-IFN IFN PEG IFN PEG IFN PEG Slower degradation by peptidases Biliary Excretion Courtesy of Peter Ferenci. Urine Excretion PegIFN alfa-2b is metabolised in the kidney, thus it is NOT to be used in hemodialysis patients as there could be accumulation of PegIFN alfa-2b, which may cause more side effects Metabolised through liver Metabolised through kidney

35 PEGASYS ® can be safely administered in patients with renal impairment Lamb M, et al. Hepatology 2001; 34: 326A *Shaded area denotes concentration of PEGASYS ® in subjects with normal renal function for both doses PEGASYS ® 135  g/week (n=6) PEGASYS ® 180  g/week (n=6) Time (hours) Mean PEGASYS ® concentration (ng/mL) Single dose

36 A number of factors influence response to therapy Host factors Race Age Gender Body weight* Insulin resistance* Substance abuse* Comorbidities* Treatment Adherence* Side effects* Type of regimen* Dose* Duration* Experience of MD* Viral factors Genotype Viral load Disease factors Coinfection* Fibrosis Cirrhosis Reasons for treatment failure * Factors which can be influenced

37 HCV treatment in end-stage renal disease ESRD patients have impaired drug absorption, distribution, metabolism and clearance leading to: ESRD patients have impaired drug absorption, distribution, metabolism and clearance leading to: Increase in adverse events 1 Increase in adverse events 1 High discontinuation rates 1 High discontinuation rates 1 Interferon-based therapies may require dose adjustment due to alterations in clearance 1 Interferon-based therapies may require dose adjustment due to alterations in clearance 1 Reducing doses of peginterferon and/or RBV may allow safe treatment of ESRD patients on dialysis 2–4 Reducing doses of peginterferon and/or RBV may allow safe treatment of ESRD patients on dialysis 2–4 RBV should not be administered to patients with creatinine clearance <50 mL/min 5 RBV should not be administered to patients with creatinine clearance <50 mL/min 5 1. Fabrizi F, et al. Hepatology 2002; 36: 3 2. Rendina M, et al. J Hepatol 2007, 46: Bruchfeld A, et al. J Viral Hepat 2006; 13: Sikole A et al. Renal Failure 2007; 29: COPEGUS ® SPC

38 Pencapaian SVR pada berbagai kelompok pasien dengan PEGASYS 1.Torriani. NEJM 2004;351: Liu et al. AASLD 2007.poster 3. Zeuzem et al.Gastroenterology 2004; 127: Kokoglu et al. J Gastroenterol Hepatol. 2006;21: Yu et al. AASLD 2007 poster 6. Kaiser et al, AASLD 2008, poster

39 Simpulan Hepatitis C merupakan salah satu penyebab sirosis hati dan kanker hati Pegylated interferon (Peg-IFN) dan ribavirin merupakan baku emas terapi hepatitis C kronik Tujuan utama terapi hepatitis C ialah tercapainya SVR (Sustained Virological Response) Capaian SVR untuk hepatitis C pada populasi pasien CKD dengan HD cukup tinggi meskipun tidak setinggi pada populasi pasien tanpa CKD Peg-IFN α-2A adalah obat terpilih untuk Hep C pada pasien HD karena diekskresikan terutama di hati

40 SAATNYA LAWAN HEPATITIS

41 28 JULY

42 SAATNYA LAWAN HEPATITIS 28 JULI

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