kuliah hepatitis2

8/12/2019 KULIAH HEPATITIS2

1/103

HEPATITIS

Dr.ALI IMRON YUSUF,SpPD, KGEH - FINASIM

DIVISI GASTRO-HEPATOLOGI-ENDOSCOPYBag-Ilmu Penyakit Dalam F.K.UNILA

RSUD Dr. Abdul Moeloek

Bandar Lampung


2/103

Hepatitis AkutInflamasi akut dari hati

Waktu < 6 bulan

Histopatologi

KausaVirus hepatitis A,B,C,D,E, G,TTX Y Z ?

Obat-obatan

AlkoholMetaboli k

Toksin

Bakteri,jamur dst.


3/103

Hepatitis atau sakit kuning

penyebab :

virus hepatitis

Penyakit infeksi yang menyerang organ

hati


4/103

Hepatitis dikenal beberapa

macam :

Hepatitis A

Hepatitis B

Hepatitis C

Hepatitis D

Hepatitis E

Hepatitis G


5/103

HEPATITIS VIRUS

SEMENTARA DI INDONESIA BARU 4

JENIS YAITU A , B, C DAN E, YANG

BANYAK DI LAPORKAN. PENELITIANLAIN BELUM BANYAK.


6/103

PENULARAN

SECARA ENTERIK : A DAN E

MELALUI DARAH : B,C,D ,G DAN TT.


7/103Hoofnagle 1994; Linnen et al.1996

PENULARAN HEPATITIS

Hepatitis Cara penularan

A Oral melalui makanan atau minuman yg tercemar

B Darah/cairan tubuh dan ibu ke bayi

C Darah/cairan tubuh dan ibu ke bayi

D Darah/cairan tubuh (hanya bila bersama VHB)

E Oral melalui air yang tercemarG Darah


8/103

TRANSMISI -ENTERIK

VIRUS TANPA SELUBUNG

TAHAN TERHADAP CAIRAN EMPEDU

DITEMUKAN DI TINJA

HUBUNGAN DGN KHRONIK TDK ADA

TDK TERJADI VIREMIA YANG LAMA


9/103

Gejala Hepatitis Akut

Rasa tidak enak diperut

Mual sampai muntah

Nyeri dan rasa penuh pada perut sisi

kanan atas

Kadang-kadang disertai nyeri sendi

Setelah 1 minggu timbul gejala utama


10/103

Hepatitis Akut Ikterik (klasik)

Stadium prodromal

FASE TIMBULNYA KELUHAN PERTAMA SAMPAITIMBULNYA IKTERUS. Gejala seperti terserang flu (Flu like sindrome),lesu berupa

demam,nyeri otot atau sendi,mual,anoreksi,diare dan kadang2konstipasi bisa terjadi.

Berlangsung 57 hari sampai 2 minggu

Stadium ikterik Bak seperti teh pekat, mata kuning,kadang ada gatal, gejala prodromal

berangsur hilang,selera makan membaik. Pada pemeriksaan fisikdidapatkan ikterik,scratch effect,hepatomegali lunak,nyeri tekan

Lab. SGOT dan SGPT meningkat > 10 kali UNL.Bilirubinmeningkat terutama yang direk.GGT dan AP meningkat

USG: hepatomegali,dark liver,penebalan dinding k.empedu

Berlangsung antara 14 minggu Stadium konvalesen

Ikterik berkurang sampai hilang, badan lebih segar

Biasanya berlangsung 3 x masa ikterik ( 2-3 MG)

A: - 9 mg, B - 16 mg.

PADA HEPATITIS B, 5-10 % MENJADI KRONIS.

MENJADI FULMINAN SEKITAR < 1%.


11/103

Anti-HAVpositive

Anti-HAV,IgM-positive

AcuteHepatitis A

Anti-HEVpositive

AcuteHepatitis E

Anti-HBc positiveHBsAg positive

AcuteHepatitis B

Anamnesis(drugs, inhabitansof Southernregions)

Anti-HDVpositive

AcuteHepatitis B and D

Anti-HCVpositive

Anti HCV-

confirmationtest

*)

AcuteHepatitis C

Anti-HCVnegative

Repeat

after6 weeks

Anti-HCV-

positive

Acute Hepatitis

*) Differential diagnosis : First diagnosed phase of a chronic hepatitisC


12/103

Hepatitis Akut

Terapi: Tidak ada terapi khusus, kecuali pada intoksikasi

parasetamol yaitu dengan asetil sistein. Hentikan obatyang diduga sebagai penyebab drug induced hepatitis

Istirahat sampai bilirubin < 2,5 mg%

Bila masih mual diberikan diit rendah lemak, bila seleramakan sudah baik diberi diit biasa

Obat hepatoprotektor

- HEPATITIS C dapat diberikan interferon @.

Prognosis tergantung etiologi

Pencegahan Kebersihan lingkungan dan perilaku hidup sehat

Vaksinasi untuk hepatitis A dan B


13/103

HEPATITIS A Virus RNA , Picorna virus

Penyebaran diseluruh dunia

Penularan fekal oral

Di Indonesia penduduk usia > 18 th lebih dari 80 % sudahpernah terinfeksi

Masa Inkubasi : 15 -30 hari ,rerata 30 hari

Masa infektif 2 minggu sebelum gejala muncul sampaidengan 3 minggu setelah ikterik

Marker serologik : Infeksi akut IgM anti HAV

Pernah terinfeksi IgG anti HAV

Pengobatan: Terapi supportif,istirahat,sampaibilirubin < 2 mg%

Pencegahan: Vaksinasi

Kebersihan lingkungan


14/103

Clinical course

In over 99% of cases, hepatitis A heals spontaneuslywithin 3 months

In less than 0.1%, fulminant hepatis occurs Jaundice is observed in approx. 90% of cases In more than 95% the transaminase curves have one

peak; there is a rapid return to normal

No transition to chronic active hepatis is observed Liver cirrhosis without floridity can develop fromfulminant hepatitis

Intensive medical care is indicated with fulminanthepatitis Strict bed rest is not necessary on medical grounds in

cases which are not complicated

Therapy


15/103

Prophylaxis

Prophylaxis by active vaccination available for travel toendemic regions The initial 1 ml injection should be followed by further

injections at 2 to 4 weeks and 6 to 12 months The success rate for vaccination is more than 95%

Passive inoculation with gamma globulin preparations(0.1 ml/kg body weight or 5.0 ml I.m.) is now only rarelyindicated

It is not usually successful in domestic circumstances,since infection has already occurred

Measures to improve hygiene are urgently recommendedto prevent further spread

In third-world countries, strict observance of hygienerecommendations and active vaccination are the bestprophylaxis.


16/103

penyakit infeksi yang disebabkanoleh virus hepatitis B yang

menyerang hati

Dapat bersifat :

* akut

* menahun (sebagian kecil

dapat berlanjut menjadi

sirosis/kanker hati)


17/103

Hepatitis B

Diperkirakan ada 350 juta penderita

penderita Hepatitis B Kronik di dunia.

75 % dari jumlah tersebut berdomisili diAsia Tenggara dan Afrika.

Indonesia tergolong daerah dengan

endemisitas menengah - tinggi ( 4 - 17 % ).


18/103

RoW

Asia Pacific

75%

75% of long-term

carriers live in Asia

Pacific

4

Hepatitis B Adalah Masalah Kesehatan

Seluruh Dunia

350 juta penderitakronis di seluruhdunia1

25-40% akanmeninggal akibathepatitis B ataukomplikasinya1,2

Sekitar 2 juta orangmeninggal setiaptahun akibat infeksiVHB, merupakanpenyebab kematian ke9 di seluruh dunia31


19/103


20/103


21/103

PREVALENSI HEPATITIS B

di KELURAHAN KALIANYAR - JAKARTA

Anti HBc Ag positif : pria 48,6%

wanita 40,7%

HBsAg positif : pria 3,5%wanita 2,1%

HbeAg positif : pria 2%

wanita 0,9%

HBV DNA positif : pria 0,4%

wanita 0,9%

H titi B T i l i


22/103

Hepatitis B Terminologi

Diagnosis

HBsAg protein dari lapisan kulit virus

HBeAg protein virus yg dihasilkan bila virusbereplikasi

Anti HBsAg zat anti yg dibentuk untukmelawan virus hepatitis B (petandasesorang sudah immun/kebal)

HBV DNA materi genetik virus hepatitis B

ALT/AST enzyme hati (proteins)-terdeteksidengan kadar tinggi dalam darah bilasel hati rusak

Histology sample jaringan hati yg dilihat dibawah mikroskop untuk menilaikerusakan hati


23/103

Perjalanan Klinis InfeksiVirus Hepatitis B Menahun

Infeksi didapat pada masa dewasa

Tahap Replikasi Tahap Nonreplikasi

HBV-DNA

ALT/SGPT serum

HBeAg positif AntiHBe postif


24/103

Slide courtesy of A. S. F. Lok, MD.

Fase Infeksi Hepatitis Kronis

HBeAg+ HBeAg-/anti-HBe+(precore/core promoter variants)

HBV DNA

Immune

Tolerance

Immune

Clearance

Low Replicative

Phase

Reactivation

Phase

200,000 - 2 x 109IU/mL

< 2000 IU/mL

> 2000 IU/mL

2 x 108-2 x 1011IU/mL


25/103


ALT

HBV DNA

Normal/mildCH

Moderate/severe CH Moderate/severe CHNormal/mild CH

Cirrhosis

Immune

Tolerance

Immune

Clearance

Low Replicative

Phase

Reactivation

Phase

Cirrhosis

< 2000 IU/mL

> 2000 IU/mL

Inactive cirrhosis

2 x 108-2 x 1011IU/mL



200,000 - 2 x 109IU/mL


26/103


ALT

HBV DNA

Immune

Tolerance

Immune

Clearance

Low Replicative

Phase

Reactivation

Phase

200,000 - 2 x 109IU/mL

< 2000 IU/mL

> 2000 IU/mL

2 x 108-2 x 1011IU/mL




27/103


ALT

HBV DNA

Normal/mildCH


Cirrhosis

Immune

Tolerance

Immune

Clearance

Low Replicative

Phase

Reactivation

Phase

Cirrhosis

< 2000 IU/mL

> 2000 IU/mL

Inactive cirrhosis

2 x 108-2 x 1011IU/mL



200,000 - 2 x 109IU/mL

Inactive-carrier state HBeAg-chronic hepatitis

HBeAg+chronic hepatitis


28/103


ALT

HBV DNA

Normal/mildCH


Cirrhosis

Immune

Tolerance

Immune

Clearance

Low Replicative

Phase

Reactivation

Phase

Cirrhosis

< 2000 IU/mL

> 2000 IU/mL

Inactive cirrhosis

2 x 108-2 x 1011IU/mL

Phases of Chronic HBV Infection


200,000 - 2 x 109IU/mL

Inactive-carrier state HBeAg-chronic hepatitis

HBeAg+chronic hepatitis


29/103

Lai CL, et al. Lancet. 2003:362:2089. Lok AS, et al. Gastroenterology. 2001:120:1828.

Profil Klinis Infeksi HBV KronisImmune

Tolerant

Immune

ClearanceHBeAg+ CHB

Inactive

HBsAgCarrier

Reacvitation

(HBeAg- CHB,Precore Mutant)

HBsAg + + + +

HBeAg + +

Anti-HBe

+ +

ALT Normal Normal

HBV

DNA

> 20,000 IU/mL

(> 105

copies/mL)

> 20,000 IU/mL

(> 105

copies/mL)

< 200 IU/mL

(< 103

copies/mL)

> 2000 IU/mL

(> 104

copies/mL*)

HistologyNormal/mild Active Normal Active* Pendapat ahli bervariasi mengenai nilai ini


30/103

agaimana Virus Hepatitiserkembang iak danmenimbulkan kerusakan didalam Hati


31/103

Sistem kekebalan tubuh tidak cukup kuat membentuk Anti Bodi

untuk melawan virus hepatitis B menahun/kronik

Penyebab Hepatitis B Kronik

Gagal meresponkeberadaan virus

dengan baik

Faktor Tubuh

Jumlah virus banyak

Jenis virus beragam

Faktor Virus


32/103

Perjalanan virus

A. Aliran darah ke

otak

B. Paru-Paru

C. Jantung

D. Hati

E. Limfa

MediaTransmisi Masuk ke tubuh sel hati


33/103

HBsAgenvelopes

Partially

double-

stranded DNA

A(n)

Infectious

HBV virion

(-)-DNA

Infectious

HBV virion

mRNAcccDNA

DNA polRT

Encapsidated

pregenomic

mRNA

HBsAgenvelopes

Partially

double-

stranded DNA

A(n)

Infectious

HBV virion

(-)-DNA

Infectious

HBV virion

mRNAcccDNA

DNA polRT

Encapsidated

pregenomic

mRNA


34/103

Sistem kekebalan

Tubuh mendeteksi

Keberadaan virus

Virus

masuk ke

sel hati

Sel Hati

Membunuh virus dengan

menyerang sel hati yang

terinfeksi

Berkembang biak


35/103

Sel Hati

Sel hati hancur

SGPT/ALT

meningkat

Membunuh virus dengan

menyerang sel hati yang

terinfeksi


36/103

VIRUS HEPATITIS B NON SITOPATIK

KERUSAKAN SEL IMUN BAIK SELULERMAUPUN HUMORAL

ADA GANGGUAN IMUN TERJADI INFEKSI KRONIK

SELAMA INFEKSI AKUT YANG BERPERANSEL RADANG LIMFOSIT T (SEL NK & T ) .

ANTIGEN VIRUS + GLIKOPROTEIN HLA class 1MENGAKIBATKAN SEL LISIS OLEH LYMPOSIT T.

HEPATITIS B YG BERLANJUT KRONIK O.K. RESPONSELULER INI TERHADAP INFEKSI VIRUS TIDAKBAIK.

RESPON TIDAK EFEKTIF UNTUK ELIMINASI VIRUS.

PATOGENESIS HEPATITIS B

KRONIK

I t


37/103

AST

HBsAg

HBeAg

IgM HBc

HBe

HBs

Icterus

0 4 8 12 16 20 24

Weeks after infection

The course of acute type B hepatitis. HBsAg=hepatitis B surface antigen; HBeAg =hepatitis Be antigen; AST = aspartate transaminase; IgM HBc = IgM antibodyagainst hepatitis B core antigen; Hbe = antibody against hepatitis e antigen;

HBs = antibody against hepatitis B surface antigen


38/103

Gejala Utama

Bagian putih pada mata tampak kuning

Kulit seluruh tubuh tampak kuning


39/103

- Selera makan hilang

- Demam tidak tinggi


40/103

Air seni berwarna coklatseperti teh


41/103

Cara Penularan

Secara vertikal

Secara Horizontal


42/103

Secara Vertikal

Dari ibu pengidap virus Hepatitis B ke bayi

yang dikandung/dilahirkan


43/103

Secara Horizontal

Dari pengidap virus melalui :

- Hubungan sex


44/103

Secara Horizontal


- Penggunaan alat suntik yang tercemar


45/103

Secara Horizontal


- Tatto


46/103

Secara Horizontal

Dari pengidap virus melalui :- Tusuk jarum (akupuntur)

- Transfusi darah

Penggunaan pisau cukur dan sikat gigi

bersama-sama, dsb


47/103

Bagaimana Penularan

Virus Hepatitis B Asia Pasifik :sebagian terbesar tertular

pada saat lahir1, 9 dari 10 yang tertular

virus hepatitis B akan tetap terinfeksisampai dewasa2

Bagian dunia yang lain: virus hepatitis B

lebih sering menular pada masa remaja

atau dewasa melalui kontak seksual atau

terpapar darah/cairan tubuh yang

tercemar.1

1Margolis et al1991; 2Thomas 1996

Cara penularan HBV di


48/103

Cara penularan HBV di

IndonesiaTranfusi dan

transplantasi organ

Berganti pasangan

seksual

Pekerja kesehatan

Bayi dengan ibu HBsAg +

Pemakai obat I

Napi & penghuni asrama/

panti


49/103

Kelompok Resiko Tinggi

Bayi dari ibu pengidap virus Hepatitis B

Dokter gigi, dokter, perawat, bidan dan

petugas laboratoriumAnggota keluarga pengidap

Kaum homoseks, para tunasusila, dan

pelanggan mereka

Pecandu obat bius dengan suntikan


50/103

Kelompok Resiko Tinggi (lanj)

Mereka yang rawan luka, misalnya

prajurit

Mereka yang sering mendapatperawatan tusuk jarum/ cuci darah

Mereka yang sering mendapat transfusi

darah


51/103

Ditentukan dengan:

HBsAg (+) > 6 bulan

Kemudian dilakukan pemeriksaan lanjutan meliputi:

Marker Biokimia : ALT/AST Marker Serologi : HBeAg / Anti HBe

Marker Virologi : HBV DNA

Marker Histologi (apabila diperlukan)

Diagnosis Hepatitis B Kronik

Di i H titi B K i


52/103

Diagnosis Hepatitis B Kronis

Anamnesis/ wawancara dan pemeriksaan badan

Pemeriksaan darah perlu dilakukan karena

sebagain besar orang tanpa gejala

Test darah

HBsAg (petanda virus)

Replikasi virus (HBV DNA dan HBeAg )

Kerusakan hati (liver enzymes - ALT/AST)

Sample jaringan hati (hati) dapat menentukan

luas atau beratnya kerusakan hati


53/103

Akibat Penyakit :

Sembuh

Meninggal karena Hepatitis Fulminan

(ganas) Menjadi Carrier (pengidap) yang

menjadi sumber penularan bagi orang

banyak Berkembang menjadi pengerasan hati

dan berlanjut menjadi kanker hati

Perkembangan Infeksi Virus


54/103

Perkembangan Infeksi Virus

Hepatitis B

InfeksiBaru

Pejamu jangkapanjang

Sembuh

15-30

tahun

Hepatitislanjut

Sembuh

Sirosis

Sirosis

SirosisAsimptomatik

Death

KankerHati

Death


55/103

15 - 30 Years

Progression of Hepatitis B

Infection

Short-termInfection

Long-termHepatitis

Cirrhosis LiverCancer

Death

Long-termCarrier

Resolution

Cirrhosis

Resolution

Death

SilentCirrhosis


56/103

Healthy Liver Hepatic Fibrosis


57/103

Healthy Liver Hepatic Fibrosis

Cirrhosis Liver Cancer

Upaya Pencegahan


58/103

Upaya Pencegahan

Program Pemerintah telah mencakup

seluruh bayi lahir di Indonesia pertahunkira-kira 4.8 juta bayi lahir setiap tahun

Kecenderungan menjadikronis mencapai 90 %

jika infeksi terjadi pada

bayi dari ibu yangmenderita Hepatitis B


59/103

Pencegahan Hepatitis B

Infeksi VHB dapat dicegah pada individu yang

belum terinfeksi dengan vaksinasi. Untuk mereka

yang sudah ter infeksi cara ini tak ada gunanya

lagi

Vaksinasi terdiri dari 3 kali suntikan yaitu 0, 1

dan 6 bulan

Vaksinasi ini efektif pada lebih dari 90%penerima.

Sampai 1998, 80 negara sudah melaksanakan

program vaksinasi


60/103

Upaya Pengobatan

Tirah baring

Diet

Obat-obatan


61/103

Obat-obatan :

Supportive : membantu pemulihangejala klinis dan laboratorium

Antivirus : Interferon (perinjeksi

Entecavire

Telbivudine

lamivudine


62/103


63/103

Pertama kali digunakan untukpengobatan penyakit HIV/AIDS

Sejak tahun 1998 sudah digunakan

secara luas untuk pengobatan Hepatitis B

Epivir-HBV (USA)

Heptovir (Canada)

Zeffix (Hongkong, Malaysia, Thailand,dll)

- Pengobatan oral yang pertama dan efektifuntuk pengobatan Hepatitis B kronis

Oral

Nyaman

Cukup sekali sehari


64/103

Epidemiology

The prevalence of antibodies against the hepatitis Cvirus is 0.4-0.9% in Germany and the Netherlands and

1.4-3.8% in Italy and Spain

In some studies antibodies were found much more oftenin men than in women

Contamination can be very high in subpopulations :Hepatitis C antibodies were found in 75% of a tribe onthe Solomon Islands

Hepatitis C antibodies are 8% to 15% more frequent inhigh-risk groups such as homosexuals or HIV-positive

patients than in the corresponding average population Blood and blood products are a certain mode of

transmission, whereas other transmission routes are not

confirmed


65/103

Epidemiology

There is a low 3% risk of accidental inoculation bysyiringe, which can probably be explained by the lownumber of hepatitis C viruses in the blood

There are only single observations available on verticaltransmission

According to more recent studies, the risk oftransmission during sexual intercourse is very low, asdemonstrated by studies of couples in which neitherpartner belonged to a high-risk group

By contrast, up to 15% of the partners of I.v. drugabusers or homosexuals are anti-HCV-positive

The results on positive anti-HCV tests in family members

of anti-HCV-positive patients are contradictory, wich thedata ranging from 0.5% to 15% The way of transmission is generally not clear The incubation period is from two weeks to over six

months.


66/103

Structure

The causative agent of hepatitis C is a singlestranded RNA virus which belongs to the flavi-family of viruses

Houghton et al. Were able to identify andcharacterize this virus using molecular-biologicalmethods

Via in vitro translation they managed to expressantigenic structures and develop a testing systemfor demonstrating hepatitis C-specific antibodies

No electron-optical pictures on the hepatitis C virusexist

This is because of the low virus count in the serum,which only reaches 106 CID (chipanzee-infectivedoses) in exceptional cases

Single-strand RNA has a length of approx 10000nucleotides


67/103

Structure

Comparisons of sequences show that nucleic acidanalyses conducted in the USA and Japan coincide

with each other to only 75%, and on the protein

level to more than 85%

Protein have similar antigenic characteristics,however, so they can be demonstrated using the

same tests

Tests performed so far have enabled identificationof three structure proteins : two surface proteins

and one nucleocapsid protein Apart from these there are four proteins whose

functions as yet remain unclear.


68/103

Diagnostics

Antigen proof : Direct demonstration of antigens isnot possible

This is due to the low number of viruses in theserum of the infected person, which is less than 105

perml and is thus below the sensitivity ofimmunologic tests

Antibodies : Second and third generation enzymeimmunological tests (ELISA) with a combination ofvarious antigens are used for demonstration ofantibodies specific for hepatitis C virus antigen

The second generation recombinant immunoblottests(RIBA) may be used for confirmation In this test system, the antigen-antibody reaction

for the various antigens used can be readseparately on a test strip


69/103

Diagnostics

There are apparently patients who have evidence ofhepatitis C virus RNA in the liver but are anti-HCV-negative, which makes it advisable to use otherantigens for the detection of HCV-specificantibodies

RNA demonstration : The polymerase chainreaction and pre-linked reverse transcription enablethe RNA of the hepatitis C virus to be demonstratedin the serum

Sensitivity is theoretically one RNA sequence perindividual test array

HCV-RNA detection detection is recommended foranti-HCV patients who have chronic active hepatitisand are scheduled for -interferon therapy.

A semiquantitative determination of HCV-RNA inthe serum is possible with various methods


70/103

Therapy

There is no specific therapy for acute hepatitis C The initial response rate to interferon- in chronichepatitis C is 45%, then 20% after one year,regardless of wether therapy was stopped after 6months of continued

Virus elimination is observed in only a portion ofpatients.

There are no large-scale controlled studies on thesuccess rates of passive immunization No active immunization exists.

Prophylaxis


71/103

Structure

The hepatitis B virus is a DNA virus which belongs to thehepadnaviruses

It is 42 nm in diameter

The surface of the virus consists of 3 different(surface)antigens

The nucleocapsid protein is associated with the DNAand the product of the P-gene (see diagram)

The Hbe antigen is sequence-homologous to large parts

of the HBcAg The DNA is 3200 bases long depending on the subtype

and is of a circular, partially double-stranded form

The sequence has been decobed


72/103

Diagnostics

Second generation test procedures have greatlyimproved specificity compared with first generationtests, making false-positive and false-negative teststhe exception

Inaddition, high gamma globulin concentrationsand paraproteins only lead to incorrect results in

exceptional cases It is now possible to differentiate various hepatitis

C virus subtypes using immunological methods,although the tests are not yet available for routinediagnostic use

In the case of autoimmune hepatitis, anti-HCVevidenced by the ELISA test (Ortho) becomesnegative again in most patients afterimmunosuppressive therapy and normalization ofthe IgG concentrations


73/103

Diagnostics

Findings obtained hitherto point to the followingconclusions :* Only 17-25% of patients positive for anti-HCV

according to ELISA are actually found to havetransmission in the end, but al serums in whichHCV-RNA was found were infectious

* Not all patients in whose serum HCV-RNA isfound are also positive for anti-HCV

* A negative anti-HCV result in the ELISA test doesnot exclude infectivity : Only 56% of patientswith post-transfusion hepatitis who later had

seroconversion were given blood that waspositive for anti-HCV* Serum samples can contain HCV-RNA although

they are positive in the anti-HCV ELISA test andnegative in the RIBA test


74/103

Titre course of hepatitis C infection

Antibodies can be demonstrated using second andthird generation tests after 4-6 weeks, although insame cases this may be delayed for 4-9 months

Seroconversion more than a year after infection isthe exception

In accordance with the tendency of the course ofhepatitis C to chronicity, there is also demonstra-tion of antibodies over a long period

Thus, in the case of 15 patients with chronic post-transfusion hepatitis the antibodies disappeared ineach one patient only after 1.5, 2, and 11 years

With acute sporadic hepatitis which is very difficultto diagnose the antibody titres of 10 of 16 patientshad dropped below the threshold value 6 monthsafter onset of the disease


75/103

Anti-HCV with chronic active hepatitis and livercirrhosis

The role of hepatitis C virus infection as thecausative agent of various chronic liver diseases hasnot yet been clarified

A possible reason for this is the false-positiveresults following raised gamma globulin

concentration Antibosies against the hepatitis C virus are reported

between 62 and 77% of cases with chronic activehepatitis non-A, non-B

There are reports of between 11% and 42% withprimary biliary cirrosis

The polymerase chain reaction test failed todemonstrate HCV-RNA in the serum of any of thepersons tested, however


76/103

Clinical manifestation

The clinical course of hepatitis C is characterized bychronic courses in 30-90% of cases and bydevelopment of liver cirrhosis in 5-30%.

This large variance in the results can parly beexplained by the inclusion of chronic hepatitides,and partly by a varying proportion of hepatitides

which heal rapidly and spontaneously It must be remembered with this data that in most

cases the patient sample is taken from specialoutpatient groups

Typical for the hepatitis C virus infection is a strong

fluctuation of aminotransferase activities by factor10 within a few days, as observed by Wiese et al. In188 female patients who acquired the HCV infectionin the course of anti D prophylactic treatment (table1).


77/103

Clinical manifestation

With chronic post-transfusion hepatitis, hepatitis C specificantibodies were found in an overage of 80% of cases (60-100%) according to several study groups

It must be remembered, however, that these data are nottaken from prospective studies but from a clientele ofspecial outpatient groups, which means that the findingsmay be too high.

Table 1.

Behavior pattern of acute attacks of hepatitis C

n %Monophasic 28 15Biphasic 42 22Multiphasic 112 52

Plateu-shaped 6 3

according ti Wiese et al. 1989


78/103

Anti HCV with chronic active hepatitis an livercirrosis

Anti HCV was evidenced in 7% of patients withprimary sclerosing cholangitis

Anti HCV was found in between 33% and 86% ofpatients with autoimmune hepatitis

Some authors described a dependency on the IgGconcentration, others saw a connection with the

simultaneous presence of antibodies against class I

liver and kidney microsomes (LKM-1)

Anti-HCV was found in up to 67% of cases withcryptogenic liver cirrhosis

Even with alcoholic liver cirrosis, anti-HCV wasobserved in up to 27% of cases.


79/103

FATTY LIVER DESEASE

Dr.ALI IMRON YUSUF,SpPD

DIVISI GASTRO-HEPATOLOGI-ENDOSCOPY

Bag-Ilmu Penyakit Dalam F.K.UNILA

RSUD Dr. Abdul Moeloek

Bandar Lampung


80/103

PENDAHULUAN

Fatty liver (perlemakan hati) : non alkoholik dan

alkoholik Fatty liver desease.

Ludwig dkk (1980) memperkenalkan istilah nonalcoholic steato-hepatitis/NASH untuk gambaran

histopatologi hati yang menyerupai hepatitis

alkoholik tetapi bukan peminum alkohol.

Saat ini istilah yang disetujui untuk semuaspektrum kelainan perlemakan hati metabolik

adalah Non-Alcoholic Fatty Liver Disease

(NAFLD).


81/103

NAFLD adalah jumlah etanol yang

dikonsumsi < 70 gram/minggu bagi wanita

dan < 140 gram/minggu bagi pria. Spektrum NAFLD mulai dari penemuan

histopatologi steatosis steatohepatitis

sirosis hati dan stadium akhir penyakit hati.NASH merupakan bentuk yang paling

serius dari NAFLD.


82/103

NAFLD penting dalam implikasi klinis

karena:

a. penyebab terbanyak dari peningkatantransaminase di Amerika

b. peningkatan prevalensi kelainan

perlemakan hatic. potensial berkembang menjadi sirosis

hepatis dan karsinoma hepatoseluler.


83/103

EPIDEMIOLOGI

Prevalensi NAFLD 17-33 % sedangkanNASH 5.7-16.5 %.

NASH telah menjadi masalah global.Banyak dilaporkan di USA,Jepang,AsiaTenggara dan Timur Tengah.

Kecenderungan adanya pertumbuhan

populasi, kenaikan prevalensi obesitas dandiabetes akan meningkatkan insidensi danprevalensi di Asia Pasifik.


84/103

NON ALCOHOLIC STEATO HEPATITIS

Penimbunan jaringan lemak dalam hati

yang jumlahnya melebihi 5%,kira2 pada

biopsi hati di temukan minimal 5-10 % sel

lemak dari hepatosit Faktor risiko

Obesitas, DM , Hiperlipidemi,Hipertensi

Gejala Peningkatan SGPT dan GGT bahkan bisa

menimbulkan hepatitis atau sirosis


85/103

PATOGENESIS

RI + gangguan supresi lipolisis perifer oleh

insulin jumlah asam lemak bebas

(FFA)

trigliserida dan

diekspor sebagai

VLDL.

First Hit

Jika tidak seimbang steatosis hati

HATI

( reesterifikasi

melalui

mitochondrial fatty

acid -oxidation)


86/103

PATOGENESIS

Selain resistensi insulin, untuk

perkembangan menjadi NASH ( Two Hit

Hypothesis), ditemukan adanya stresoksidatif yang menyebabkan peroksidasi

lipid (Second Hit). Kadar petanda stres

oksidatif yaitu serum thioredoxin pada

pasien NASH lebih tingi bermakna daripada

dengan perlemakan hati saja.


87/103

PATOGENESIS

Peranan Sitokin

Pada subjek dengan obesitas, beratnya penyakit

hati dan resistensi insulin berhubungan dengankadar TNF-di jaringan lemak dan hati.

Toksisitas Lipid

Peningkatan asupan FFA dapat menimbulkan efek

sitotoksik langsung terhadap sel hati. Mekanismetidak langsung yang penting adalah peroksidase

lipid asam lemak tidak jenuh.


88/103

FAKTOR RESIKO

Resistensi Insulin/Sindrom Metabolik

Resistensi insulin berperan penting dalam

patofisiologi NAFLD dan bahkan RI jugaterjadi pada pasien NAFLD dengan berat

badan normal dan toleransi gula darah

normal.Pasien NAFLD yang disertai sindrom

metabolik lebih cenderung mempunyai

NASH.


89/103

FAKTOR RESIKO

Obesitas

Lemak viseral dan bukan lemak total:

prediktor penting untuk perlemakan hati danjuga untuk hiperinsulinemia, penurunan

ekstraksi insulin hati dan resistensi insulin

perifer.


90/103

FAKTOR RESIKO

MENGURANGI BERAT BADAN,

TERUTAMA DENGAN DIET DAN

OLAH RAGA TUJUAN : UNTUK MENGOREKSI

RESISTENSI INSULIN DAN

MENGURANGI OBESITAS SENTRAL.


91/103

MANIFESTASI KLINIS

MAYORITAS TANPA GEJALA

SEBAGIAN MENGELUH LEMAH,

MALAISE,RASA TDK ENAK DANMENGGANJAL DIPERUT KANAN

ATAS

SEBAGIAN DITEMUKAN SECARAKEBETULAN PADA USG.


92/103

GAMBARAN KLINIS

Usia 40-50 tahun dengan kenaikantransaminase yang ditemukan secarakebetulan.

Obesitas, DM, hiperlipidemia, hipertensidan resistensi insulin.

Umumnya asimtomatik, dirujuk karena

peningkatan transaminase. Lelah, rasa tidak nyaman di abdomen kanan

atas


93/103

PEMERIKSAAN FISIK

Tidak ditemukan stigmata penyakit hati

menahun.

Hepatomegali pada 50% pasien.


94/103

DIAGNOSIS

GOLD STANDART BIOPSI

NON INVASIF DENGAN USG DAN

KIMIA DARAH, SAAT INI SEDANG DIKEMBANGKAN.


95/103

PEMERIKSAAN


96/103

PEMERIKSAAN

LABORATORIUM

SGOT/SGPT walaupun < 4X nilai normal

Kadar albumin serum, bilirubin, studi koagulasi

dalam batas normal kecuali penyakit sudah

progresif.

Hiperlipidemia, DM

Kadar besi serum termasuk ferritin

NAFLD dapat ditemukan pada kelainan hati lain

seperti hepatitis virus B dan C, hepatitis autoimun,

sirosis bilier primer, dan defisiensi -1 antitripsin.


97/103

PENCITRAAN

ULTRASOUND (US), gambaran ekogenikdifus bright liver.

Computerized tomography (CT) MRI

Ketiga pencitraan di atas mempunyaisensitivitas yang baik untuk mendiagnosisNAFLD salama deposit lemak di hati>30%, tetapi tidak ada yang mampumembedakan steatosis dari NASH.


98/103

BIOPSI HATI

Saat ini biopsi hati merupakan standar baku

untuk diagnosis dan mrupakan satu-satunya

cara untuk membedakan NASH daristeatosis dengan atau tanpa inflamasi.


99/103


100/103

MANAGEMENT

PENGONTROLAN FAKTOR RESIKO

TERAPI FARMAKOLOGIS


101/103

FARMAKOLOGIS

ANTI DIABETIK DAN SENSITIZER

ANTI HIPERLIPIDIDEMIA

ANTI OKSIDAN

HEPATOPROTEKTOR


102/103

TERAPI MEDIKAMENTOSA

Obat meningkatkan sensitivitas insulin

metformin

Antioksidan

Vit E, C, betaine dan N-acetylcystein

Obat menurunkan lipid

clofibrate, gembrozil, dan atorvastatin.

THANKS FOR YOUR


103/103

THANK S FOR YOUR

ATTENTION

BANDAR LAMPUNG

OKTOBER 2O12

kuliah hepatitis2

Documents