Kuliah Pengantar

Ilmu Gastroentero-Hepatologi

Penyakit Dalam

________________________

Dr. H. Syafruddin AR. Lelosutan, Sp.PD

Departemen Penyakait Dalam RSPAD GS

ANATOMI SISTIM DIGESTIVUS (The alimentary tract.)

Parotid gland

Salivary glands

HATI

SIRRHOSIS HEPATIS

Berat hati : 1,2 1,5 kg

Faal hati : metabolisma,

sintesis,

detoksifikasi,

regulasi endokrin,

sistim RES,

sistim koagulasi

DEFINISI :

Hepatitis = keradangan hati

PENYEBAB :

1. Infeksi : parasit (malaria, amoeba),

bakteri (tbc, banal), jamur,

viral (hepatitis A, B, C, D, E, F, TT, CMV, EBV)

2. Kerusakan hati : alkohol, obat-obat (asetaminofen, metildopa, INH, fenitoin, valproat, CPZ, amiodaron, TMP-SMZ, eritromisin), bahan beracun

3. Autoimun

4. Fibrosis kistik

5. Penyakit Wilson : deposit Cu berlebihan dalam hati

Viral Hepatitis

Source of

virus

Route of transmission

Chronic

infection

Prevention

Feces

Fecal-oral

No

Vaccine, immune globulin

A

Type of Hepatitis

Blood/ body fluids

Yes

Vaccine, immune globulin,

Childbirth, needles,

sex, transfusion

B

Blood/ body fluids

Yes

Blood donor screening,

risk management, education

Needles, transfusion,

sex, childbirth

C

Feces

Fecal-oral

No

Ensure safe

drinking

water

E

Blood/ body fluids

Yes

Needles, sex, transfusion

(requires HBV co-infection)

D

HBV vaccine

CDC fact sheets, available at www.cdc.gov

RIWAYAT RINGKAS HEPATITIS B.

SAKIT KUNING : (+) sjk abad 5 SM di Babilonia.

Hippocrates (460-375 SM) icterus infectiosa menular >< imunisasi.

Letupan wabah di kalangan militer :

- Franco-Prussian War (1870) - Perang Boer (1948)

- Perang Korea (1952) - Perang Timur Tengah (1956)

Lurman (1885) : epidemi hepatitis virus di Bremen dengan transmisi parenteral.

Water viral hepatitis, wabah di : Inggris (1895), Skandinavia (1916, 1944), New Delhi

(1955-1956).

Flaum (1926) : epidemi hepatitis virus pada penderita DM yang mendapat obat suntikan.

Blumberg BS (1977) : penemu virus hepatitis B (HBV) Australian antigen = HBsAg (Lihat gambar I.).

Adi Teruna Effendi (1982) : Hepatitis virus merupakan penyakit jabatan pada kalangan

profesi kesehatan, risiko tertular lebih tinggi 2-10 kali dibanding populasi umum.

New York State Workmens Compensatoir Bureau (1984) : mengakui hepatitis virus sebagai penyakit jabatan pada kelompok petugas kesehatan

Prevalence of HBV

Hepatitis B virus (HBV) is one of the worlds most common infectious diseases

Around 400 million people have chronic HBV

infection

> 1 million people die every year of HBV-

related chronic hepatitis, cirrhosis or liver

cancer

WHO 1998; Lai et al Lancet 2003

1. Penemuan pertama kali jenis infeksi, dengan sebutan virus hepatitis Non-

A Non-B dan didukung pembuktian klinis 2. Diidentifikasi sebagai virus hepatitis C (HCV) dan dikembangkan di

California tahun 1988.

3. Gambaran klinis berhubungan dengan riwayat transfusi darah, dengan masa inkubasi 2-26 minggu. 4. HCV : virus dengan amplop ukuran 50 nm genom RNA positif mengandung 9400-9500 nukleotida, mirip Flavivirus dan Pestivirus

(PRINCE,et al.1974; FEINSTONE,et al.1974

SULAIMAN, 1996)

Riwayat ringkas

Prevalence of HBV and Incidence of

Hepatocellular Carcinoma (HCC)

World prevalence of HBV carriers

HBsAg carriersprevalence

8%

Poorly documented

Annual incidence of primary HCC

Cases/100,000 population

13 310 10150 Poorly documented

WHO 1999

Characteristics of HBV and HCV

Double stranded DNA

virus

4 open reading frames

High vireamia

High infectivity

Integrates into host

genome

No cytotoxicity

Single stranded RNA

virus

1 open reading frame

Low viraemia

Low infectivity

No integration into host

genome

Cytotoxicity (?)

HBV HCV

PATOGENESIS

HEPATITIS VIRAL

Averett DR and Mason WS. Viral Hep. Rev. 1995; 1:12942

Clinical hepatitis

HBV or HCV -infected

hepatocytes

Inflammation and cell death

HBV or HCV

production

Hepatocyte regeneration

Uninfected hepatocytes

Infection

Immune response

Re-infection

Alcohol, co-infection

etc.

Viral replication

Transplant or

Death

Immune response

Tissue damage

Scarring

HCC

Cirrhosis

Evidence of disease

PATOGENESIS

HEPATITIS VIRAL KRONIK

Adapted from Dr Z Goodman, Armed Forces Institute of Pathology, Washington, DC

Host and environmental factors (e.g. alcohol, co-infection)

Perjalanan Klinis HEPATITIS :

Penyakit Hepatitis akut kronik FAILURE

Komplikasi kegagalan hati :

Sirosis hati :

hipertensi portal varises esofagus : pecah HEMATEMESIS MELENA

hipoalbuminemia asites : SBP

Hepatoma : HCC (diffuse parenchymal)

Lobulated hepatoma

Ensefalopati hepatikum Sindroma hepatorenal

Faktor risiko dan Gejala

FAKTOR RISIKO HEPATITIS

VIRAL KRONIK

1. IDU (pemakai obat suntik), Tatoo

2. Overdosis asetaminofen, alkohol atau obat lain

3. Kebiasaan seksual risiko tinggi / freesex

4. Terkontaminasi : family, travel, eating, living

5. Resipien : - transfusi darah sblm th. 1990, - transplantasi organ

6. AIDS

7. Bayi dengan ibu pengidap Hepatitis B atau C

8. Pekerja Kesehatan, Dentists and Dental Hygienists

PENATALAKSANAAN.

Diagnostik :

Klinis, Laboratoris dan Biopsi Hati.

Terapeutik :

Pencegahan.

Pengobatan / medikamentosa.

Edukasi :

Diagnostic of Hepatitis B

Viral markers

HBV-DNA, HBsAg, HBeAg, Anti-HBs,

Anti-HBe and Anti-HBc.

Other markers

ALT (SGPT), Liver histology, Clinical

examination, Ultrasound.

Importance of Serum Markers

Diagnostic of Hepatitis C

HCV antibody tests

enzyme immunoassays (EIA)

recombinant immunoblot (RIBA)

HCV-RNA tests

Qualitative: AMPLICOR HCV Test [50 IU/mL]

Quantitative: AMPLICOR MONITOR Test [600

IU/mL]

Assessing Predicting

Length Response Sustained

Method Screen Confirmation of Therapy to Therapy Response

ALT/AST X

Enzyme X

immunoassay (EIA)

Supplemental assay X

(RIBA*)

HCV RNA qualitative X X

assay

HCV RNA quantitative X X

assay

HCV genotype X

NIDDK. Chronic hepatitis C: current disease management.

Utility of Diagnostic Tests

*No longer widely used.

Role of Liver

Biopsy in HCV

Infection

Confirm clinical diagnosis

Assess severity of

fibrosis and

necroinflammation1,2

Evaluate possible

concomitant disease

processes (eg,

alcoholic liver disease,

NASH)1,2

Assess

therapeutic

intervention1

1. NIH Consensus Statement Online. Management of hepatitis C.

2. British Liver Trust Information Service. A guide to liver function tests.

Terapi Pencegahan :

Menjaga dan meningkatkan Daya Tahan Tubuh.

Menghindari :

- pemakaian jarum suntik berulang-ulang.

- seks bebas

- transfusi darah sembarangan

Memelihara higiene-sanitasi.

Imunisasi / Vaksinasi (untuk HBV).

Terapi Medikamentosa :

Averett DR and Mason WS. Viral Hep. Rev. 1995; 1:12942

Block HBV or HCV production and/or re-

infection with antiviral

therapy

Clinical hepatitis

HBV or HCV -infected

hepatocytes

Inflammation and cell death

HBV or HCV

production

Stimulate immune response with interferon

Hepatocyte regeneration

Uninfected hepatocytes

Infection

Lysis of infected hepatocytes and regulation

of viral replication

Immune response Alcohol,

co-infection etc.

CAM

with Hepatoprotektor/stimulator

Pilihan Obat :

INTERFERON : IFN Standar

Peg-IFN

ANTIVIRAL : Ribavirin

NUKLEOSIDA

ANALOGUE : Lamivudine

Adevofir dipivoxil

IMMUNE SUPPORT : Glicirrhizine

Thymosin

HEPATOPROTEKTOR :

FLEBOTOMI : LIT DI RSPAD GS

Kapan dinyatakan sembuh dari

serangan infeksi Hepatitis

Serangan akut HBV : HBsAg (+), IgM anti HBc (+).

HCV : sulit diidentifikasi.

Kondisi kronis HBV : Anti HBc total (-) HBsAg (+)

HBeAg (+) aktif HCV : Anti HCV (+).

Keadaan sembuh HBV : HBsAg (-), Anti HBs (+), HBV DNA (-)

HCV : Anti HCV (-), HCV RNA (-)

Adalah :

Proses pengerasan parenkhim hati akibat nekro-inflamasi yang

berlarut-larut/kronik

Cirrhotic = pengerasan, batu

PARENKHIM

HATI

inflamasi nekrotik

HEPATOMA

CIRRHOSIS HEPATIS

BERBAGAI

PENYEBAB

fibrotik

SIRRHOSIS HEPATIS

Drug Induced

Hepatitis

Viral Hepatitis

Fatty Liver/

Steato Hepatitis

Nodul-nodul

GEJALA DAN TANDA

GEJALA : Cepat lelah, mengantuk siang hari,

tidak bisa tidur malam hari. Ngomong ngaco.

TANDA-TANDA :

Badan kurus, perut membuncit (ascites),

muntah darah (hematemesis), tremor, berak darah warna hitam/coklat marun (melena), kesadaran berkabut

(encefalopati)

LABORATORIUM :

Hiperglobulinemia (rasio Alb/Glob terbalik)

Trombositopenia

KLASIFIKASI KLINIS

SIROSIS HATI

LATEN/TERKOMPENSASI

SIROSIS HATI DEKOMPENSATA

Klasifikasi CHILDs-PUGH SKOR 1 2 3

Albumin (g/dL) > 3.5 2.8 - 3.5 < 2.8

Ascites None Mild Marked

Bilirubin (umol/dL) < 3.4 3.4 5.0 > 5.0

Ensefalopati None Mild Marked

PT (s prolonged) < 4 4 6 > 6

Nilai SKOR : Jika jumlah angka

Childs A : < 7

Childs B : 7 9

Childs C : > 9 the poorest prognostic group, is less than 12 months

Hayes, et al. Churchills Pocketbook of Medicine, 3rd Edition. China, 2002.

KOMPLIKASI SIROSIS HATI

HEMETEMESIS MELENA

ASITES

SINDROMA HEPATORENAL

HEPATOMA

KOMA HEPATIKUM

Epidemiologi :

Kanker hati banyak didapatkan di daerah

Timur Jauh dan Afrika.

Penyebab utama : infeksi Hepatitis B dan

C

Di Indonesia sering disertai oleh Sirosis

Hati

Gejala dan Tanda:

Bervariasi

Berlangsung perlahan-lahan

ikterus

Nyeri epigastrium

Rasa tidak enak pada perut kanan atas

BB menurun

Asites hemorrhagik

Diagnosis :

Laboratorium : AFP (alfa feto protein)

USG :

CT-scan

Angiografi

Biopsi hati