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Departemen Ilmu Penyakit Dalam

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


3 Hepatitis C 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) 80-90% kasus menunjukkan gejala dan tanda yang minimal, kecuali bila komplikasi telah terjadi (pada tahap lanjut)  “silent killer”

4 Infeksi HCV: Masalah Global
Infeksi HCV: Masalah Global ! ( Di Dunia: 170 juta orang terinfeksi HCV ) Di AS: ± 4 juta orang Di Indonesia: ± 4 juta orang WHO Wkly Epidemiol Rec 2000;75:18-19. 4

Country Prevalence in general population Prevalence in dialysis population* reference (year) Netherlands 0.1% 3% 1998 Italy 0.5% 22.5% 1999 Belgium 0.9% 9.4% Bulgaria 1.1% 65.8% France 16.3% 2000 Turkey 1.5% 31.4% USA 1.8% 10% 2003 Saudi Arabia 57% 2001 Moldavia 4.9% 75% Egypt 18.1% 80% Fabrizi F et al. Hepatology 2002 *Infection of dialysis patients via nosocomial transmission

6 Infeksi HCV: Masalah Global
Distribusi Geografis Genotipe HCV: 1a, 1b a, 2b, 2c, 3a 1a, 1b 2a, 2b, 3a 2a 1b 4 1b, 6 1b, 3a 4 Slide 6. HCV Infection: Worldwide Genotype Distribution Isolates of HCV are classified according to the genetic relatedness of their nucleotide sequences (ie, genotype).1,2 The geographic epidemiology of HCV genotypes worldwide is depicted in this slide. HCV genotype 1 is by far the most frequently occurring genotype worldwide (40% to 80%). Genotypes 1a and 1b are most prevalent in the United States and genotype 1b in Europe, Turkey, Japan, Taiwan, and Australia.1 HCV genotype 2 is widely distributed throughout the nations of the West and the Far East, but has a lower prevalence (10% to 40%) than genotype 1.1,3 HCV genotype 3 also occurs throughout the West and the Far East. Genotype 3 is also prevalent in Australia.1,3 HCV genotype 4 is prevalent in Africa and the Middle East and accounts for more than 90% of HCV infections in Central Africa and the majority of infections in the Middle East.1,3 HCV genotype 5 is prominent in southern African nations, where more than 50% of infections are genotype 5. Genotype 6 has been reported predominantly in Southeast Asia (eg, Hong Kong, Macau).1,3 Proposed HCV genotypes 7 to 11 are thought to be subtypes of genotypes 1 to 6.3 HCV genotypes are clinically relevant in terms of diagnostics, impact on natural history of liver disease, treatment regimen required, and response to interferon (IFN) treatment.1 1. Fang JWS et al. Clin Liver Dis. 1997;1: Simmonds P. Hepatology. 1995;21: Hepatitis C Council of South Australia Inc. Hepatitis C genotypes. 3b 1a, 1b, 2b, 3a 1b, 3a 5a Indonesia: a+1b: 60 – 65% a: 17 – 26% Fang JWS et al. Clin Liver Dis. 1997;1: 6

7 Penyakit sistemik bukan hanya hati yang menanggung!

8 Didiagnosis menderita Hepatitis C
INFEKSI HCV GLOBAL: Fenomena Gunung Es! Didiagnosis menderita Hepatitis C < 10% Diobati simtomatik 170 juta orang telah terinfeksi (di Indonesia 4 juta) kasus baru/tahun 4,1% dari seluruh kasus karsinoma meninggal/tahun > 90% asimtomatik Tidak terdiagnosis 8 (Sulaiman A, Selayang pandang Hepatitis C, 2004) 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 Hepatitis C National Surveillance data 2009) Study of chronic hepatitis C prevalence in health care professionals, 2008


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

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) Slide 13. Risk factors for HCV infection The predominant risk factor for the transmission of HCV infection is intravenous drug abuse through transfer of infected blood by sharing of syringes and needles. In the United States, as many as 90% of users are infected with HCV after 5 years of injection drug abuse.1 Approximately 80–90% of transfusion-associated hepatitis cases considered “non-A, non-B” were recategorised as HCV after 1990 when Michael Houghton and colleagues cloned HCV. Since the introduction of tests to detect the presence of HCV in blood, the risk of acquiring HCV infection as a result of a transfusion has been reduced to 1 in Today, the risk of receiving HCV-infected blood products or transplanted organs from an infected donor is negligible in areas where blood and organ donors are screened for the virus. Vertical transmission of the virus from an infected mother to an infant is considered to be low risk (5–6%),1 however this risk is increased to around 20% in HIV–HCV co-infected mothers.3 Patients receiving chronic haemodialysis therapy are also considered low risk (10%). Household transmission (through percutaneous/mucosal exposure to blood and sharing of contaminated personal items such as razors, toothbrushes, nail-grooming equipment) can also occur but is rare. Additionally, certain occupations involve risk of HCV transmission, including healthcare, emergency medical, and public service work. Combined, these modes of HCV transmission account for an additional 10% of cases.1 In the remaining 10% of patients with HCV infection, the source of the infection has not been identified, although many individuals in this category are in low-economic strata. Other factors of unproven or low risk include body piercing or tattooing and intranasal cocaine use.1 Residency in areas that do not maintain precautions against transmission of blood-borne diseases can be considered a risk factor. Therefore, in developing countries, the majority of HCV transmission occurs through use of unsterilised injection equipment and unscreened blood transfusion.4 Although the role of sexual activity in HCV transmission remains undefined, 20% or less of HCV-infected individuals report sexual exposures in the absence of percutaneous risk factors.1 According to the Centers for Disease Control and Prevention (CDC) Sentinel Counties Study, early sexual activity, nonuse of condoms, presence of other sexually transmitted diseases, multiple sex partners, and traumatic sex can be risk factors.5,6 1. CDC. MMWR 1998; 47: 1 2. NIH Consensus Statement Online. Management of hepatitis C 3. National Institutes of Health. Hepatology 2002; 36: S3 4. WHO. Fact Sheet 5. Alter M. Hepatology 1997; 26 (3 suppl 1): 62S 6. CDC. Hepatitis C slide kit. September 25, 2000

14 Hubungan seks berisiko suntikan tattoo
tindik narkotika transfusi 14 Hubungan seks berisiko suntikan tattoo 14


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

17 17 17

18 Kegunaan Uji Diagnostik
Menilai Prediksi Lama respon “Sustained Penilaian Skrining Konfirmasi Terapi terapi Response” SGPT/SGOT X Anti-HCV by Enzyme X immunoassay (EIA) Supplemental assay X (RIBA*) for anti-HCV HCV RNA qualitative X X assay HCV RNA quantitative X X assay HCV genotype X Slide 18. Utility of Diagnostic Tests A number of diagnostic tests are employed for screening patients for the presence of HCV infection, for assessing the viral load, and for determining their response to antiviral therapy. Measuring biochemical indicators of HCV such as alanine transaminase (ALT) and aspartase transaminase (AST) is not sufficient to establish a diagnosis of HCV. The enzyme immunoassay (EIA), which is used to detect the presence of anti-HCV, is recommended as the initial test for patients with clinical liver disease and is also acceptable for screening at-risk patients. The high sensitivity and specificity rates offered by third-generation EIAs have eliminated the need for a confirmatory recombinant immunoblot assay (RIBA). EIAs, however, can occasionally yield false-positive results. To confirm the diagnosis, testing for serum HCV RNA by sensitive polymerase chain reaction (PCR) amplification is recommended. Prior to initiating treatment in patients infected with CHC, it is important to determine patients’ baseline viral load with a quantitative assay as well as their HCV genotype. HCV genotype determines the length of therapy and, together with viral load, is predictive of treatment response. While on treatment, patients’ progress can be monitored by determining the presence of HCV RNA, first with a qualitative PCR assay and then, in cases of positive HCV RNA, with a quantitative PCR assay to assess treatment response and to predict the length of therapy and treatment outcome. NIDDK. Chronic hepatitis C: current disease management. *Tidak lazim dipakai lagi NIDDK. Chronic hepatitis C: current disease management.

19 Kriteria Diagnostik Infeksi HCV:
Hepatitis C Akut 1. Diketahui paparan < 6 bulan* 2. Anti-HCV positif / negatif 3. HCV RNA positif 4. SGPT meningkat * 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 Panel of biochemical markers, e.g. FibroTest Ultrasonography, FibroScan Liver biopsy Gold standard for grading inflammation and disease stage Slide 20. Tests of liver function

21 Tujuan Terapi Hepatitis C
Tujuan primer = “sembuh” Virus “lenyap”1 Stop perkembangan penyakit Hilangkan gejala Tujuan Sekunder Cegah fibrosis1 Cegah terjadinya sirosis2 Cegah Gagal Hati Cegah Kanker Hati2 Kriteria kesembuhan dalam praktek  bila tercapai SVR (Sustained Virological Response) Worman HJ. Hepatitis C: current treatment. 2. Peters MG et al. Medscape HIV/AIDS eJournal. 2002;8(1).

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

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

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

25 Terapi Hepatitis C Kronik : Perkembangan Selama >10 tahun
100 80 PEG-IFN + Ribavirin 48 weeks 54-63% 60 IFN + Ribavirin 48 weeks 42% % Sustained vriologic response 40 PEG-IFN 48 weeks 25-39% IFN 24 weeks 48 weeks 6% 16% 20 1991 2009

26 Interferon inhibits the virus AND enhances the immune response
100% Lymphocyte HCV RNA Inhibition of viral replication Slide 26. Interferon inhibits the virus AND enhances the immune response The time course of virological response to interferon in patients with chronic hepatitis C can be characterised as a biphasic decline in HCV RNA levels. During the first phase – the induction phase – interferon therapy induces early viral clearance from circulating blood by inhibiting HCV cellular replication. Additionally, degradation of free virus occurs in the initial stages of the induction phase in interferon responders.1 The response to interferon therapy in this phase is dose dependent.2 During the second, or maintenance, phase, which begins approximately 14 to 28 days after the initial dose of interferon and continues throughout the treatment period, the immune system begins to eliminate HCV-infected cells.1 The goal of interferon maintenance therapy is clearance of HCV-infected cells, which is dependent on the length of the treatment period.    1. Ferenci P, et al. Viral Hep Rev 1999; 5: 229 2. Neumann A, et al. Science 1998; 282: 103 Immune system elimination of infected cells Induction phase Maintenance phase Detection limit 0% 14–28 Days ? 1st dose Ferenci P, et al. Viral Hep Rev 1999; 5: 229

27 Side effects of treatment
Experience of side effects varies between individuals Side effects are reversible and appear to be dose dependent Side effects can be managed Dose reduction is a common management strategy Referral to the multidisciplinary team as necessary Psychiatrist or psychologist or counsellor Dietician Social worker The side effects of treatment vary between individuals. Some people experience all the side effects while others have limited side effects. These symptoms are rarely severe and appear to be dose related and reversible. It is important to emphasise that the side effects can be successfully managed, in most circumstances and only rarely is treatment ceased. However, dose reduction is a common management strategy. The level of dose reduction depends on the severity of effect and should always be ordered in consultation with the specialist and/or hepatology nurse. Referral to members of the multidisciplinary team is important to ensure the patient receives expert care and can continue treatment. For example, if the patient is experiencing mental health concerns – referral to a psychiatrist (for medication) or psychologist or counsellor for behavioural management strategies. If the patient has decreased appetite and is losing weight, referral to a dietician may provide support and strategies to improve nutritional intake. If the patient is experiencing fatigue and their activities of daily living are being affected, referral to a social worker may create access to home help, meals on wheels or other community services; and access to Centre Link payments. ASHM Hepatitis C s100 prescriber course 3.4 27

28 Most common side effects of interferon treatment
Flu-like symptoms Fever, chills Headache Fatigue or asthenia Myalgia, arthralgia Cough Nausea Anorexia Diarrhoea Pruritus Rash Weight loss Psychiatric symptoms Depression Insomnia Alopecia Injection-site reaction Leukopenia Thyroiditis Autoimmunity Thrombocytopenia Slide 28. Most common side effects of interferon treatment A wide range of clinical symptoms and laboratory abnormalities have been associated with interferon treatment. Adverse reactions include flu-like symptoms (headache, fatigue or asthenia, myalgia, arthralgia, fever, chills), nausea, anorexia, diarrhoea, psychiatric symptoms (depression, insomnia), alopecia and injection-site reactions. Interferon treatment may also result in leukopenia, thyroiditis, autoimmunity and thrombocytopenia. 1. INTRON® A. PDR® 2. ROFERON®-A. PDR®

29 Most common side effects of ribavirin treatment
Haemolytic anaemia Teratogenicity Cough and dyspnoea Rash and pruritus Insomnia Anorexia Slide 29. Most common side effects of ribavirin treatment Treatment with ribavirin has also been associated with a number of adverse events, including haemolytic anaemia, cough, dyspnoea, rash, pruritus, insomnia, ataxia, anorexia and teratogenicity.1,2 1. REBETOL®. PDR® 2. Chutaputti A. J Gastroenterol Hepatol 2000; 15(suppl): E156 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 14 6 Ikatan protein Ikatan uretan tidak stabil Ikatan amida stabil Slide 30. Differences between the two currently available pegylated interferons The two currently available pegylated interferons, PEGASYS® (40KD) and pegylated interferon alfa-2b (12KD), differ significantly in their chemical structure. PEGASYS® consists of interferon alfa-2a monopegylated with a 40KD branched polyethylene glycol (PEG) molecule. The four major positional isomers are Lys31, Lys121, Lys131 and Lys134. Ninety-four percent of the PEG attachment takes place at these four sites. The remaining ~6% of the PEG attachment takes place at Lys70 and Lys83. The amide bond between PEG and interferon alfa-2a is stable.1 Pegylated interferon alfa-2b (12KD) is formed by attaching a 12KD PEG molecule to interferon alfa-2b. Fourteen different positional isomers have been identified.2 The predominant site of pegylation is the His34 residue (~50%) with the remaining positional isomers located at various lysines, the N-terminal cysteine, serines and tyrosines.2,3 The bond between the PEG molecule and the histidine residue is labile.3,4 1. Bailon P, et al. Bioconjugate Chem 2001; 12: 195 2. Grace M, et al. J Interferon Cytokine Res 2001; 21: 1103 3. Youngster S, et al. Curr Pharm Des 2002; 8: 2139 4. Wang Y-S, et al. Biochemistry 2000; 39: 10634 1. Bailon P, et al. Bioconjugate Chem 2001; 12: 195 2. Kozlowski A, et al. BioDrugs 2001; 15: 419 3. Wang Y-S, et al. Biochemistry 2000; 39: 10634 4. Youngster S, et al. Curr Pharm Des 2002; 8: 2139 5. Grace M, et al. J Interferon Cytokine Res 2001; 21: 1103

31 Volume distribusi PEG-IFN a-2a (40KD) kecil
PEGASYS® (Peginterferon Alfa-2a [40KD]) tidak perlu disesuaikan dengan berat badan Volume distribusi PEG-IFN a-2a (40KD) kecil Slide 31. PEGASYS® (Peginterferon Alfa-2a [40KD]) Need Not Be Dosed by Weight PEGASYS® (peginterferon alfa-2a [40KD]) has a restricted distribution and is predominantly found in the bloodstream and interstitial fluid rather than in the tissues.1 Its volume of distribution is small (8 to 12 L).2 Because its maximum tolerated and minimum effective doses are widely separated, PEGASYS® has a broad therapeutic index.1 In an analysis of patient variability in volume of distribution and clearance of PEGASYS® in relation to body surface, body weight, and body mass index, body weight accounted for less than 1% of the observed between-patient variability in these pharmacokinetic parameters.1 Moreover, the efficacy and safety of PEGASYS® are not altered by variations in patient body weight.1 1. Lamb MW, Martin NE. Ann Pharmacother. 2002;36: Perry CM, Jarvis B. Drugs. 2001;61: 180 mg 180 mg 180 mg Lamb MW, Martin NE. Ann Pharmacother. 2002;36:

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
Small linear PEG-IFN PEGASYS® (40KD) (Stable Bond) Metabolised through kidney PEG Metabolised through liver PEG IFN IFN Absorption 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 Urine Excretion PEG IFN PEG IFN BLOOD Slower degradation by peptidases Rapid degradation by peptidases Biliary Excretion Courtesy of Peter Ferenci.

35 PEGASYS® can be safely administered in patients with renal impairment
PEGASYS® 135 mg/week (n=6) Single dose PEGASYS® 180 mg/week (n=6) 18 16 14 12 10 concentration (ng/mL) Mean PEGASYS® 8 Slide 35. PEGASYS® can be safely administered in patients with renal impairment Lamb and associates provided evidence that PEGASYS® (peginterferon alfa-2a [40KD]) can be administered safely in patients with renal impairment. These investigators treated 24 haemodialysis patients with end stage renal disease (ESRD), but without chronic hepatitis C, with single doses of 45, 90, 135, or 180 g /week PEGASYS®. Results for subjects who received either 135 or 180 g/week PEGASYS® (shown here) indicated only slightly higher plasma concentrations than those for individuals with normal renal function. These single-dose results demonstrate an acceptable safety profile for PEGASYS® in patients with ESRD. The 30% reduction in total body clearance in these individuals is in keeping with the observation that PEGASYS® is mainly cleared by liver metabolism. The study results also indicate that therapeutically effective concentrations of PEGASYS® can be achieved in subjects with ESRD with once-weekly doses of 135 or 180 g/week. Lamb M, et al. Hepatology 2001; 34: 326A 6 4 2 24 48 72 96 120 144 168 Time (hours) * Shaded area denotes concentration of PEGASYS® in subjects with normal renal function for both doses Lamb M, et al. Hepatology 2001; 34: 326A

36 A number of factors influence response to therapy
Host factors Race Age Gender Body weight* Insulin resistance* Substance abuse* Comorbidities* Viral factors Genotype Viral load Reasons for treatment failure Slide 36. A number of factors influence response to therapy Disease factors Coinfection* Fibrosis Cirrhosis Treatment Adherence* Side effects* Type of regimen* Dose* Duration* Experience of MD* * 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: Increase in adverse events1 High discontinuation rates1 Interferon-based therapies may require dose adjustment due to alterations in clearance1 Reducing doses of peginterferon and/or RBV may allow safe treatment of ESRD patients on dialysis2–4 RBV should not be administered to patients with creatinine clearance <50 mL/min5 Slide 371. HCV treatment in end-stage renal disease Patients with end stage renal renal disease (ESRD) suffer from increased adverse events and high discontinuation rates. This is due to impaired drug absorption, distribustion, metabolism and clearance. Therefore interferon-based therapies may require dose adjustment due to alterations in clearance.1 Safe treatment of patients with ESRD may be achieved by reducing the doses of PEGASYS® (peginterferon alfa-2a [40KD]) and ribavirin.2–4 Rendina et al.: Patients received PEGASYS® 135 µg/week plus COPEGUS® (ribavirin) 200 mg/day for 24 or 48 weeks (genotype non-1 and 1, respectively). The dose of ribavirin was tailored according to plasma concentrations and to haemoglobin levels. Outcomes in treated patients were compared with those of a matched untreated control group: Drop-out rate– 14% 34 out of 35 (97%) treated patients achieved an SVR compared with 0 out of 35 patients in the untreated control group (0%) (p<0.001).2 Bruchfeld and colleagues: 2 patients received 135 µg/week PEGASYS® and 4 patients received 50 µg/week peginterferon alfa-2b (12KD). The dose of ribavirin was reduced to 200–400 mg/day. Patients were treated for 24 weeks (genotype 2) or 48 weeks (genotype 1 and 4): 4 out of 6 patients completed (or nearly completed) therapy. 3 out of 6 patients achieved an SVR. Two patients were treated with PEGASYS® (peginterferon alfa-2a [40 KD]) plus ribavirin for 36 and 24 weeks, respectively; 1 patient was treated with pegylated interferon alfa-2b (12KD).3 Sikole et al.: 14 patients (infected with HCV genotype 1 or 4) received 135 μg/week PEGASYS® after the dialysis session for a period of 48 weeks: Overall, 2 (14.3%) patients discontinued treatment because of insufficient therapeutic response. Overall, 3 patients (21.34 %) discontinued treatment because of serious adverse events. SVR was achieved in 36% of the patients (5/8 patients) at the end of the follow-up.4 Ribavirin 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: 768 3. Bruchfeld A, et al. J Viral Hepat 2006; 13: 316 4. Sikole A, et al. Renal Failure 2007; 29: COPEGUS® SPC 1. Fabrizi F, et al. Hepatology 2002; 36: 3 2. Rendina M, et al. J Hepatol 2007, 46: 768 3. Bruchfeld A, et al. J Viral Hepat 2006; 13: 316 4. Sikole A et al. Renal Failure 2007; 29: COPEGUS® SPC

38 Pencapaian SVR pada berbagai kelompok pasien dengan PEGASYS
Torriani. NEJM 2004;351: Liu et al. AASLD 2007.poster 3. Zeuzem et al.Gastroenterology 2004; 127: 4. 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


41 28 JULY


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