Hepatitis Virus, Sirosis Hati

dan Hepatoma (HCC)

Ummi Maimunah

Div. Gastroentero-Hepatologi
Dep-SMF Ilmu Penyakit Dalam
FKUA / RSUD Dr Soetomo
 THE LIVER
• FUNCTIONS OF THE LIVER:
– MAKES PROTEIN: NEEDED FOR
BLOOD CLOTTING
– STORES: VITAMINS, IRON AND
GLYCOGEN
– METABOLIZES / produce energy :
SUGAR, PROTEIN AND FAT
TO PRODUCE ENERGY
– DETOXIFICATION

2
THE LIVER
• ENZYMES (PROTEINS) FROM
LIVER (CALLED LFT’S – LIVER
FUNCTION TESTS) eg:
– ALT (SGPT)
• ALANINE
AMINOTRANSFERASE
(Serum Glutamic Pyruvat
Transaminase/
– AST (SGOT)
• ASPARTATE
AMINOTRANSFERASE
(Serum Glutamic
Oxsaloacetic transaminase)

3
Tests based on detoxification &
excretory functions :
• Serum bilirubin (measured by Van Den
Bergh method)
• Urine bilirubin
• Blood ammonia
• Serum enzymes : AST, ALT, GGT (gama
glutamic transpeptidase), 5’Nucleotidase
(5NT)
Tests that measure Biosynthetic
function of liver :
Serum Albumin, Serum Globulins, PT & INR

Serum Enzymes – that reflect cholestasis:

- Alkaline Phosphatase
- 5’Nucleotidase (5NT)
- Gamma glutamyl transpeptidase (GGT)
HEPATITIS
“INFLAMMATION OF THE LIVER”
CAUSED BY:
• VIRUSES- HEPATITIS A, B, C, D, E, G
• OTHER INFECTIONS (MONONUCLEOSIS)
• CHEMICALS
– ALCOHOL
– Drud induced (eg: ACETAMINOPHEN)

6
Acute Viral Hepatitis
I. Definition:
Diffuse liver inflammation lasting less than
6 months
 II. Causes:
Hepatitis A Hepatitis B Hepatitis Hepatitis C Hepatitis E
HAV HBV D HCV HEV
Infective serum HDV Post Epidemic/
hepatitis hepatitis transfusion Entral
hepatitis
virus RNA DNA Incomplete RNA flavi firus RNA
Hepa virus RNA+HBsAg

transmission Feco-oral Paraentral and post transfusion Feco-oral

Sexual low risk 1-5 %
Intrauterine low risk <5%
Incubation 2 – 6 weeks 2 – 6 months 2 – 6 months 2 – 6 months 2 – 6 weeks
periode (4 wks) (2,5 mos) (5 mos) (0,5 – 2,5 mos)

Chronicity & no Yes Yes Yes No

liver cancer
Immunization Non specific Specific Ig Non specific
-passive Ig Ig

-active HAV vaccine Heptavax Heptavax

HBV vaccine HBV vaccine
 III. Clinical picture
1.Preicteric stage or prodromal stage : 3 – 9 days
Sudden onset of influenza like picture: fever - headache
malaise – muscular pain. Nausea & vomiting.
2.Icteric stage: 2-4 w
Jaundice with fever & improvement of general condition.
Urine is dark brown & frothy, Stool are clay in color.
3.Convalescence stage:
Signs & symptoms gradually disappear
Jaundice may persist for some times due to affinity of bile
pigment to elastic tissue
Complete recovery of liver may take up to 6 months
IV. Investigation:
• LFT:
- serum bilirubin : total, direct and indirect.
- ALT – AST : from 500 – 2000 IU/L ALT > AST.

• Urine: Early bilirubin appearance

• Stool: Pale – clay with staetorrhea,
Diminished stercobilinogen
• Serology:
Acute stage Chronic stage others
Hepatitis A Anti HAV IgM Anti HAV IgG Fecal
HAV
Hepatitis D Anti HDV IgM Anti HDV IgG
Hepatitis E Anti HEV IgM Anti HEV IgG
 Hepatitis B marker:
antigen Significance Correspon significance
ding Ab

HBsAg Appear after 6 week Anti HBs Appear after 3 m

(surface) Acute infection, remain for 3 ms Reflecting recovery &
Chronic infection if >6 ms immunity
HBcAg Detected on Liver Biopsy only Anti HBc Appear after 2 m
(core) (not serum) Reflecting sever
acute & chronic form
HBeAg Reflect ongoing viral replication Anti HBe Appear after 2.5 m
(envolop) (chronicity) Non replicating virus

HBV DNA Most sensitive indication for viral replication & chronicity (Dan particle)
It is detected by PCR

Window periode (serologicqal gap):

HBsAg (-), Anti HBs (-) & Anti HBc (+).
 Hepatitis C markers:
Marker time significance
HCV Ab After 3 – 6 ms of Exposure to infection
infection not immunity

HCV After 1 – 2 weeks Indicate active virus

RNA
 V. Course & Complication:
• Complete Recovery: Occur in most cases of virus A – E
• Chronicity: Liver Chirrosis – HCC ( Virus B , C & D)
• Fulminant hepatitis: ( Acute liver failure ) :
encephalopathy & coma, usually dies in 10 days
• Prolonged cholestasis (Cholestatic jaundice).

VI. Treatment:
Rest: Bed rest till LFT normal
Diet : CHO, Protein, Lipid
Drugs: vitamin
VII. Prophylaxis:
• Screening: of blood for hepatitis Ag , disposable syringes,
avoid sharing razors or tooth brush
• Passive prophylaxis:
Hepatitis A : serum gamma globulin
Hepatitis B: HBIG
• Active prophylaxis (Vaccin):
Hepatitis A:
Inactivated HAV 0.5 – 1 ml IM to be repeated
after 6 -12m
Hepatitis B:
Recombinant HBV vaccine (Heptavax) IM in
3 doses at 0 - 1 - 6 m
Hepatitis Kronis
Hepatitis B Kronis
 HBV: Penyebab Signifikan Morbiditas dan
Mortalitas di Dunia
• Prevalensi: > 2 miliar terinfeksi[1]
• insiden: 4 juta kasus akut / tahun[1]]

• karier kronis[1]: 350 – 400 juta

• 25% meninggal karena hepatitis kronis, sirosis, HCC[1]
• 75% Asian[2]

• penyebab 60-80% dari semua kanker hati primer (HCC)[1]

• HBV 100 kali lebih infeksius daripada HIV[4]

1. WHO. Hepatitis B. 2002. 2. Maynard JE, et al. In: Viral Hepatitis and Liver Disease. New York: Alan R.
Liss, Inc. 1988. 3. CDC. Epidemiology & prevention of vaccine-preventable diseases. The Pink Book. 8th
ed. 4. CDC. MMWR. 2001;50:RR-11.
 Distribusi HBV di Dunia

Prevalensi HBsAg
High ≥ 8%
Intermediate 2% to 7%
Low < 2%

Centers for Disease Control and Prevention. CDC Health Information for International Travel 2010.
 Dampak infeksi jangka
panjang
Sirosis
Sembuh Karier Tanpa Gejala yg Jelas

Infeksi Hepatitis Kanker RIP

Baru kronik Sirosis Hati

Pembawa Virus B Sirosis Kematian

(Karier) Jangka
panjang

15 – 30 Tahun
 Diagnosis Hepatitis B
Pemeriksaan Lab/penunjang
• Biokimia :
• ALT meningkat, IgM anti HBc sudah (-)
• HBV DNA
• Petanda kuantitatif dari replikasi virus dan khronisitas
• Serologi :
• HBeAg dan anti-HBe
• HBsAg dan anti-HBs
• Histologi :
• Menunjukkan aktifitas fibrosis dan nekroinflamasi
• USG, CT Scan
• Fibroscan.

Infeksi kronis
• Persistensi HBsAg, anti HBc,
• & serum HBV DNA terdeteksi > 6 bulan
 GEJALA

- asimtomatis
- komplikasi
- Flare/ reaktivasi.
Tujuan Terapi Hepatitis B:
Sasaran (tujuan langsung):
 Supresi persisten HBVDNA
 Serokonversi HBeAg
 Perbaikan histopatologi hati
 Normalisasi ALT

Tujuan akhir :
 Pencegahan progresivitas sirosis hati &
kanker hati
 Peningkatan kualitas hidup
 Perpanjangan kesintasan
KELOMPOK RISIKO TINGGI
• Pengguna Narkoba Suntik
• Sex aktif
• Laki-laki yang berhubungan sex sesama jenis
• Anak-anak yang berasal dari daerah endemik
• Sosial ekonomi rendah
• Kontak seksual dengan penderita Hepatitis B
• Bayi dengan ibu terinfeksi virus Hepatitis B
• Pekerja di sektor kesehatan
• Pasien Hemodialisa

Centers for Disease Control and Prevention, 2000

TUJUAN VAKSINASI HEPATITIS B

MENCEGAH :
 Transmisi virus
 Hepatitis B akut
 Penyakit hati kronik dan
cirrhosis
komplikasinya

liver cancer
 TERAPI
• 1. Interferon α ( IFN - α ) / Pegylated interveron
α-2a / α-2b
• 2. Nucleosida analog:
Lamivudine, Telbivudine, Tenovovir,
Adefovir dipivoxil, Entecavir.

• 3. Thymosin alfa I
Hepatitis C Kronis
 Introduction
• It is 130–210 million
individuals

• 3% of the world are

chronically infected HCV

• The routes of HCV infection:

blood transfusion, injection
procedures, iv drug use

• 6 HCV genotypes: 1, 2, 3, 4,
55&6
Natural History of Disease
 Prevention of HCV transmission
• Blood screening
• universal precaution
• condom for sexual partner
• Decrease drug injection (only is needed)
 Transmission
• Contaminated blood most infectious (transfusions prior to
1992, now needle-sharing, intranasal cocaine)

• Sexual transmission (less than 5%)

• Perinatal transmission (approx. 5%); dependent on maternal

viral load

• Shared razors, toothbrushes, open cuts, etcOccupational

exposure (roughly 2% with needlesticks)

• ALWAYS USE UNIVERSAL PRECAUTIONS

 Diagnosis & Pre-therapeutic assessment:
• History and Phisical examnination.
• laboratory : CBC, liver, renal, tyroid, autoantibody
• Anti HCV
• HCV RNA (Kuantitatif) and genotype HCV
• Liver biopsy is indicated
• Psychiatry evaluastiont is indicated.
• Cardiopulmonal evaluationt are indicated.
• Pregnant test

Tx: Combine  Peginterferon (inj) & Ribavirin (oral)

Goal Tx:- eradicate HCV infection

/ terjadi SVR (sustainned viral respon)
 Liver Cirrhosis

Ummi Maimunah, dr. SpPD-KGEH FINASIM

Incidence of Cirrhosis

• Tenth leading cause of death in US

• At least 25,000 deaths annually
• Higher death rates for men than women
•  mortality in African Americans and Hispanics
 What Is Cirrhosis of the Liver?

Cirrhosis is defined
histologically as a diffuse hepatic
process characterized by fibrosis
and the conversion of normal liver
architecture into structurally
abnormal nodules (diffuse
process with fibrosis and
nodule formation).

Type: micronoduler
macronoduler
mixed

Cirrhosis of the Liver

 Etiology
• Viral hepatitis B & C (tersering)

• Alcohol

• Metabolic : Iron overload

Copper overload ( Wilsons
disease )
Alpha 1 antitrypsin deficiency
Galactosemia
Tyrosinemia
 Etiology…..
 Cholestatic ( Biliary )

 Hepatic venous outflow block : Budd Chiari Syndrome

Heart Failure

 Autoimmune Hepatitis

 Toxins and Drugs ( Methotrexate, Amiodarone )

 Indian Childhood Cirrhosis

 Cryptogenic
Clinical Manifestations of the Liver
Clinical Manifestations of the Liver
GEJALA KLINIS
Asimtomatis
Kullit kuning
Capai
Lemah
Nafsu makan menurun
Gatal
Mual
Berat badan menurun
Nyeri perut
Mudah berdarah
GEJALA KLINIS
akibat komplikasi
Ikterus
asites
Perdarahan varises
Ensefalopati
Caput Medusae Ascites Palmar erythema
jaundice Esophageal varices
 DIAGNOSIS
ANAMNESIS PEMERIKSAAN FISIK

1. Konsumsi 1. Splenomegali
alkohol jangka 2. Spider telangiectasias
panjang 3. Ikterus atau jaundice
2. Narkotik 4. Asites
suntikan
5. Edema
3. Penyakit hati
menahun
4. Hepatitis virus
B atau C
 DIAGNOSIS
Laboratorium Endoskopi
1. ↑abnormal enzim Varises esofagus
transaminase (AST
CT scan (CAT) atau
dan ALT)→tanda
peradangan atau MRI dan USG
kerusakan hati. Ditemukan :
2. ↓ albumin dan faktor nodul dalam hati,
pembeku darah splenomegali, cairan dalam
3. Ditemukan abdomen
Autoantibodi: Pungsi Asites
ANA,ASMA,AMA
Mengetahui penyebab asites
KOMPLIKASI EDEMA dan
SBP
(Spontaneous
SIROSIS HATI ASITES Bacterial
Peritonitis)
(SH)
Perdarahan Ensefalopati
Varises Esofagus Hepatik

Sindroma Sindroma
Hepatorenal Hepatopulmoner

Kanker Hati
Hipersplenisme (hepatocellular
carcinoma)
 PENGOBATAN
Sirosis Hati (SH)
Mencegah Mengobati Mencegah Transplant
Kerusakan komplikasi kanker hati asi hati
hati lebih sirosis dan deteksi
lanjut dini
 Ascites

• Ascites is pathologic fluid accumulation

within the peritoneal cavity
 Ascites

 Cirrhosis : 85 %

 Malignancy : 10 %

 Tuberculous

 Cardiac cirrhosis
Examination
 Complications - Infection
• SBP
• Positive AF culture
• AF absolute PMN count (≥ 250cells/mm3)
• Absence of intraabdominal surgically
treatable source of infection
 Treatment
 Five days of parenteral 3rd generation cephalosporin
such as Cefotaxime / Amoxicillin – Clavulanic acid

 Diuretic therapy : increases total protein and ascitic

opsonic activity

 Prophylaxis : Pts who had an episode of SBP

Pts with low ascitic fluid protein (<1g/day )
Norfloxacin 400 mg / day
Trimethoprim-Sulfomethoxazole
 Hepatorenal Syndrome
• Development of renal failure in patients with severe
liver disease in absence of any identifiable renal
pathology

• 2 Types:
Type 1 HRS : progressive Rapidly (< 2 weeks )
Type 2 HRS : do not progressive
Ensefalopati Hepatik

Tidur lebih banyak siang

dari pada malam
(perubahan pola tidur)
Mudah tersinggung
Tidak mampu
konsentrasi atau
menghitung
Kehilangan memori
Bingung
Kehilangan kesadaran
secara bertahap
Koma
Kematian
 Precipitants
 ELECTROLYTE  DRUGS – Alcohol
IMBALANCE withdrawl , sedatives
 Diuretics
 Vomitings  INFECTION
 Diarrhoea  SBP
 Urinary
 BLEEDING  Chest
 Oesophageal & Gastric
varices  CONSTIPATION
 Gastro duodenal erosions
 Mallory weiss tear  LARGE PROTEIN MEAL
 Kanker Hati
(hepatocellular
carcinoma)

Nyri perut Eritrositosis

Pembengkaan Hipoglikemia
Pembesaran hiperkalsemia
hati
Penurunan
berat badan
demam
HCC
 Epidemiology

Hepatocellular carcinoma is the 5th most common malignancy

worldwide & the 3rd cause of cancer related death with male-to-
female ratio
– 5:1 in Asia
– 2:1 in the United States

Tumor incidence varies significantly, depending on geographical

location.

HCC with age.

 Etiology
• Hepatitis B
-increase risk 100 - 200 fold
- 90% of HCC are positive for (HBs Ag)

• Hepatitis C
• Cirrhosis
- 70% of HCC arise on top of cirrhosis

• Toxins -Alcohol -Tobacco - Aflatoxins

• Autoimmune hepatitis
• States of insulin resistance- Overweight in males
Diabetes mellitus
 Diagnosis
what investigations are required to make a
definite diagnosis

1) AFP produced by 70% of HCC

> 400ng/ml
AFP over time

2) Imaging:
- focal lesion in the liver of a patient with cirrhosis is highly likely
to be HCC
- Spiral CT of the liver
- MRI with contrast enhancement

3) Biopsy is rarely required for diagnosis in 1–3%.

Terimakasih