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    Slide-Diagnosis Dan Interpretasi Hepatitis B Khronik

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    Siti nur rohmah
    The document discusses hepatitis B virus (HBV) infection, including: 1. It outlines the 5 phases of chronic HBV infection according to EASL guidelines: immunotolerant phase, immune clearance phase, inactive carrier phase, HBeAg-negative chronic hepatitis phase, and HBsAg-negative phase. 2. It describes the global prevalence of chronic HBV infection and how HBV is most commonly transmitted between people. 3. It discusses the various clinical markers used to diagnose and monitor HBV infection, including serological, virological, imaging, and histological markers.

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    Slide-Diagnosis Dan Interpretasi Hepatitis B Khronik

    Uploaded by

    Siti nur rohmah
    41 views24 pages
    The document discusses hepatitis B virus (HBV) infection, including: 1. It outlines the 5 phases of chronic HBV infection according to EASL guidelines: immunotolerant phase, immune clearance phase, inactive carrier phase, HBeAg-negative chronic hepatitis phase, and HBsAg-negative phase. 2. It describes the global prevalence of chronic HBV infection and how HBV is most commonly transmitted between people. 3. It discusses the various clinical markers used to diagnose and monitor HBV infection, including serological, virological, imaging, and histological markers.

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    Slide-Diagnosis dan Interpretasi Hepatitis B khronik

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    The document discusses hepatitis B virus (HBV) infection, including: 1. It outlines the 5 phases of chronic HBV infection according to EASL guidelines: immunotolerant phase, immune clearance phase, inactive carrier phase, HBeAg-negative chronic hepatitis phase, and HBsAg-negative phase. 2. It describes the global prevalence of chronic HBV infection and how HBV is most commonly transmitted between people. 3. It discusses the various clinical markers used to diagnose and monitor HBV infection, including serological, virological, imaging, and histological markers.

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    41 views24 pages

    Slide-Diagnosis Dan Interpretasi Hepatitis B Khronik

    Uploaded by

    Siti nur rohmah
    The document discusses hepatitis B virus (HBV) infection, including: 1. It outlines the 5 phases of chronic HBV infection according to EASL guidelines: immunotolerant phase, immune clearance phase, inactive carrier phase, HBeAg-negative chronic hepatitis phase, and HBsAg-negative phase. 2. It describes the global prevalence of chronic HBV infection and how HBV is most commonly transmitted between people. 3. It discusses the various clinical markers used to diagnose and monitor HBV infection, including serological, virological, imaging, and histological markers.

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    Diagnosis dan Interpretasi

    Penanda Infeksi Virus Hepatitis B


    Putut Bayupurnama
    Div Gastroenterology & Hepatology, Dept of Internal Medicine,
    Gadjah Mada University(GMU)/Dr. Sardjito General Hospital,
    Yogyakarta, Indonesia
    Prevalensi Global Hepatitis B Kronik

    National Travel Health Network and Centre. Update 2010. Available online at : http://www.nathnac.org/
    How is HBV transmitted?
    HBV is transmitted through activities that involve percutaneous (i.e., puncture
    through the skin) or mucosal contact with infectious blood or body fluids (e.g.,
    semen, saliva), including :

    • Sex with an infected partner


    • Injection drug use that involves sharing needles, syringes, or drug-
    preparation equipment
    • Birth to an infected mother
    • Contact with blood or open sores of an infected person
    • Needle sticks or sharp instrument exposures
    • Sharing items such as razors or toothbrushes with an infected person

    HBV is not spread through food or water, sharing eating


    utensils, breastfeeding, hugging, kissing, hand holding,
    coughing, or sneezing.

    Hepatitis B Fact Sheet. July 2012. Available online at : http://www.who.int/mediacentre/factsheets/fs204/en/


    Hepatitis B General Information. June 2010. Available online at : http://
    www.cdc.gov/hepatitis/hbv/pdfs/hepbgeneralfactsheet.pdf
    Populasi dengan Risiko tinggi infeksi HBV
     Perilaku seksual yang berisiko tinggi
     Homoseksual
     Pengguna narkoba jarum suntik
     Transfusi darah, hemodialisa
     Tranplant organ padat
     Pekerja pelayan kesehatan
     Wisatawan yang berkunjung ke daerah endemik hepatitis B
     Keluarga pasien hepatitis B
     Bayi yang lahir dari ibu yang mengidap hepatitis B

    Hepatitis B Fact Sheet. July 2012. Available online at : http://www.who.int/mediacentre/factsheets/fs204/en/


    Hepatitis B General Information. June 2010. Available online at : http://
    www.cdc.gov/hepatitis/hbv/pdfs/hepbgeneralfactsheet.pdf
    Natural Clearance of HBsAg and HBeAg

    • HBsAg
    – 0.5% of carriers per year; most develop anti-HBs
    • HBeAg
    – 4% to 12% of carriers per year
    • 40% to 50% in 5 years
    • 70% to 80% in 10 years
    – More frequent in older carriers and with  ALT levels
    – Up to 20% who clear HBeAg have  1 HBeAg
    reversions

    Lok ASF, McMahon BJ. Hepatology. 2001;34:1225-1241.


    McMahon BJ, et al. Ann Intern Med. 2001;135:759-768.
    Effect of Timing of Infection

    Patients infected during


    Patients infected during
    adolescence/adulthood early childhood
    • Majority of white patients • Asian, African, some
    • No immune tolerance phase; Mediterranean patients
    disease of relatively short duration • Prolonged immune tolerance
    • Good response to and immune clearance phases
    immunomodulatory therapy • Poorer response to
    • Disease nonprogressive after HBeAg immunomodulatory therapy
    seroconversion; HBV DNA levels • Disease continues to progress
    undetectable by hybridization assays in a proportion of anti-HBe
    —“healthy carriers” patients

    Hoofnagle J, et al. Hepatology. 1987;7:758-763. Lai CL, et al. Lancet. 2003;362:2089-2094.


    Gejala Hepatitis B

     Hepatitis B Akut :
     Gejala hepatitis B akut bervariasi dari asimtomatik, ringan, hingga kasus jarang
    hepatitis fulminant
     Gejala hepatitis B akut: demam, cepat lelah, penurunan nafsu makan, mual, muntah,
    nyeri perut kanan atas, kuning (ikterik), urin berwarna gelap, tinja berwarna dempul

     Hepatitis B Kronik :
     Mayoritas pasien hepatitis B kronik asimtomatik
     Jika terjadi gejala biasanya menyerupai gejala hepatitis B akut.

    Hepatitis B FAQ for Health Professionals. CDC 2012 Available online at :


    http://www.cdc.gov/hepatitis/hbv/hbvfaq.htm
    Marker Hepatitis B Kronik

    • Marker Serologis : HBsAg, anti-HBs, HBeAg, anti-HBeAg,


    AntiHBc
    • Marker Virologis : HBV DNA
    • Marker Pencitraan : Ultrasonografi hati
    • Marker Histologis : Biopsi
    • Marker Biokimia : AST, ALT, GGT, AP, Bilirubin, serum albumin, globulin,
    darah rutin dan waktu protrombin.

    Keeffe EB, et al. Clinical Gastroenterol and Hepatol 2008


    Danta M. B Positive – all you wanted to know about hepatitis B: a guide for primary care providers
    WHO Guidelines 2017
    WHO Guidelines 2017
    WHO Guidelines 2017
    WHO Guidelines 2017
    WHO Guidelines 2017
    Marker Biokimia, Histologis, Imaging, & Skor Fibrosis

    • ALT
    • Sering dipakai untuk menilai penyakit hati dan menentukan pasien yang
    masuk dalam kandidat terapi.
    • Nilai normal 30 IU/mL (wanita), 40 IU/mL (pria)
    • Biopsi Hati
    • Dua hal yang dinilai pada biopsi hati : derajat fibrosis (METAVIR)dan nekroinflamasi.
    • Biopsi hati dapat dipertimbangkan pada pasien dengan HBV DNA meningkat
    dengan kadar ALT normal dan usia pasien diatas 35 tahun.
    • Kekurangan : invasif, tidak nyaman, mahal dan menghabiskan banyak waktu

    • Fibroscan : Skor Fibrosis 0-4


    • Skor Fibrosis
    • APRI Score; Fib-4

    Keeffe EB, et al. Clinical Gastroenterol and Hepatol 2008


    Danta M. B Positive – all you wanted to know about hepatitis B: a guide for primary care providers
    Perjalanan Penyakit Hepatitis B Kronik

    Vassilopoulos D, et al. Nature Reviews Rheumatology 8, 348-357 (June 2012)


    Fase Hepatitis B Kronik

    Terdapat lima fase pada Hepatitis B Kronik:

    1. Imunotoleransi

    2. Imunoklirens (imun
    klirens HBeAg +)

    3. Residual inaktif
    (Inaktif HBV karier)

    4. Reaktivasi (HBK HBeAg


    -)

    5. HBsAg negatif

    Kandidat Terapi Kandidat Terapi


    Liauw YF, et al. Hepatitis B virus Infection. Lancet 2009
    Papatheodoridis G, et al. J of Hepatol 2012
    Fase 1 – Fase Imunotoleransi

    • HBeAg +, kadar HBV DNA tinggi, kadar ALT normal atau rendah.

    • Nekroinflamasi ringan atau tidak ada nekroinflamasi.

    • Progresi ke arah fibrosis rendah atau tidak ada.

    • Lebih sering terjadi dan durasinya lebih lama terjadi pada individu yang
    terinfeksi perinatal atau pada tahun pertama kehidupan.

    • Pasien dalam fase ini sangat menular

    Papatheodoridis G, et al. EASL Guideline for Hepatitis B 2012. J of Hepatol 2012


    Fase 2 – Fase Imunoklirens

     HBeAg +, kadar HBV DNA lebih rendah (dibanding fase imunoklirens), kadar ALT
    meningkat atau berfluktuasi
     Derajat nekroinflamasi hati sedang atau berat
     Progresifitas fibrosis lebih cepat
     Muncul setelah beberapa tahun fase imunotoleransi.
     Lebih sering dan lebih cepat terjadi pada pasien yang terinfeksi HBV pada masa
    dewasa (maturasi imunitas spesifik anti-HBV)
     Laju HBeAg loss lebih tinggi dibandingkan fase imunotoleransi.
     Fase ini berakhir pada serokonversi HbeAg menjadi anti-HBeAg

    Papatheodoridis G, et al. EASL Guideline for Hepatitis B 2012. J of Hepatol 2012


    Fase 3 – Fase Residual Inaktif

     Kadar HBV DNA sangat rendah atau tidak terdeteksi dan kadar ALT normal
     Fase ini berkaitan dengan outcome jangka panjang yang baik dengan risiko
    sirosis atau HCC sangat rendah.
     Dapat terjadi HBsAg loss yang diikuti oleh serokonversi HBsAg menjadi anti-
    HBsAg (1-3% kasus per tahun)
     Selain itu dapat terjadi juga progresi penyakit menjadi hepatitis B kronik
    HBeAg –.
     Pasien dalam fase ini harus di monitor kadar ALT tiap 6 bulan setelah 1 tahun
    pertama dan HBV DNA secara periodik.

    Papatheodoridis G, et al. EASL Guideline for Hepatitis B 2012. J of Hepatol 2012


    Fase 4 – Fase HBK HBeAg Negatif
     Merupakan fase reaktivasi dari perjalanan penyakit alamiah hepatitis B kronik
     Reaktivasi periodik hepatitis B yang ditandai dengan terjadinya fluktuasi kadar HBV
    DNA, ALT dan munculnya gejala hepatitis akut secara periodik.
     Ditandai dengan HBeAg negatif.
     Terjadi mutasi pada regio promoter pre core dan/atau basal core sehingga tidak
    dapat mengekspresikan HBeAg.
     Kemungkinan terjadinya remisi spontan pada pasien dalam fase ini sangat kecil.
     Fase ini sulit dibedakan dengan fase residual inaktif sehingga perlu dilakukan
    pengukuran berkala HBV DNA, ALT dan monitoring gejala klinis hepatitis akut.

    Papatheodoridis G, et al. EASL Guideline for Hepatitis B 2012. J of Hepatol 2012


    Fase 5 – Fase HBsAg negatif

     Pada fase ini, kadar HBV DNA tidak terdeteksi pada serum, kadar antibodi
    anti-HBC dengan atau tanpa anti-HBs terdeteksi.
     Tercapainya HBsAg loss sebelum onset sirosis berkaitan erat dengan outcome
    yang baik dengan risiko sirosis, dekompensasi dan HCC menurun.

    Papatheodoridis G, et al. EASL Guideline for Hepatitis B 2012. J of Hepatol 2012


    EASL Guidelines
    Fig. 1
    2017

     Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II)
    HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic
    hepatitis and (V) HBsAg-negative phase- ‘‘occult HBV infection”

    Journal of Hepatology DOI: (10.1016/j.jhep.2017.03.021)


    AASLD HBV Guidelines: An Update
    clinicaloptions.com/hepatitis

    Interpretation of Serologic Results


    HBsAg Total IgM Anti-HBs Interpretation
    Anti-HBc Anti-HBc
    Negative Negative -- Negative Susceptible; offer vaccination
    Negative Positive -- Positive Immune due to natural infection
    Negative Negative -- Positive Immune due to hepatitis B vaccination
    Positive Positive Negative Negative Chronic HBV infection
    Positive Positive Positive Negative Acute HBV infection
    Negative Positive -- Negative Unclear; could be any one of the
    following:
    1. Resolved infection (most common)
    2. False-positive anti-HBc; susceptible
    3. “Low-level” chronic infection
    4. Resolving acute infection

    CDC. Hepatitis B FAQs for Health Professionals.


    Terima Kasih

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