Hepatitis: Dr. Leonardo B Dairi SPPD Kgeh
Hepatitis: Dr. Leonardo B Dairi SPPD Kgeh
Hepatitis: Dr. Leonardo B Dairi SPPD Kgeh
Parasitic
Viral
Epstein Barr Herpes Simplex Varicella Zoster Coxsackievirus Rubella Yellow Fever
Alcohol Drugs
Noninfectious
Hepatitis E virus
Hepatitis D virus Hepatitis G virus
Enterically transmitted
Coinfection with HBV Parenterally transmitted
A
NANB
Enterically E transmitted
B D
F, G, ? other
Parenterally C transmitted
A
Source of virus Route of transmission Chronic infection feces
E
feces
blood/ blood/ blood/ blood-derivedblood-derived blood-derived body fluids body fluids body fluids
fecal-oral no
Prevention
pre/postpre/post- blood donor pre/post- ensure safe exposure exposure screening; exposure drinking immunization immunization risk behavior immunization; water modification risk behavior modification
Serum bilirubin
Alanine aminotransferase (ALT) Aspartate aminotransferase (AST) Alkaline phosphatase Prothrombin time, partial thromboplastin time, platelet count, bleeding Blood count with blood smear exam
HEPATITIS A
RNA Picornavirus
Single serotype worldwide Acute disease and asymptomatic infection
No chronic infection
Protective antibodies develop in response to infection - confers lifelong immunity
An acute :
discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of appetite, nausea, vomiting), and jaundice or elevated serum aminotransferase levels Never chronic Adults often feel unwell for 6 weeks
Laboratory criteria
age group:
Rare complications:
Fulminant hepatitis Cholestatic hepatitis Relapsing hepatitis Average 30 days Range 15-50 days
Incubation period:
Chronic sequelae:
None
Infection
Response
Viremia
HAV in stool
10
11
12
13
Week
Body Fluids
Serum Saliva
Urine
100
Source:
102
104
106
108
1010
Low
Very low
MANAGEMENT HEPATITIS A No specific treatment Symptomatis Prednisolone 40mg PO daily,tapering off (24)weeks Prevention is better than cure
PREVENTING HEPATITIS A Hygiene (e.g., hand washing) Sanitation (e.g., clean water sources) Hepatitis A vaccine (pre-exposure) Immune globulin (pre- and post-exposure)
HEPATITIS A VACCINES
protective levels of antibody within 1 month of receiving first dose; essentially 100% have protective levels after second dose
Highly efficacious In published studies, 94%-100% of children protected
38,157
94% (79%-99%)
New York
2-16 yrs
1,037
100%
(85%-100%)
At least 5-8 years among adults and children No cases in vaccinated children at 5-6 years of follow-up
Efficacy
Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years Other mechanisms, such as cellular memory, may contribute
HEPATITIS B
HBV
HBV
Acute / fulminant Inactive carrier state Chronic Hepatits Liver cirrhosis Hepatocellular Carcinoma.
4.6-8.0
4.4-13.0 4.0
Prevalensi HBsAg
High ( 8%) Intermediate (2% to 8%) Low (< 2%) Mast EE, et al. MMWR Recomm Rep. 2006;55:1-33. Custer B, et al. J Clin Gastroenterol. 2004;38(10 suppl):S158-S168.
2.6-5.1
2.4-4.7 1.4-8.0
US
0.2-0.5
8 genotypes (A-H) :
and
More advanced liver disease Lower response rate to interferon Greater risk of HCC development.
HBV nomenclature
HBV: hepatitis B virus HBsAg: hepatitis B virus surface antigen HBcAg: hepatitis B virus core antigen
Domain Reverse transcriptase/ DNA polymerase mengalami overlap dengan gen permukaan Ditemukan dalam darah dan cairan tubuh cccDNA
(+) (-)
1622
MMWR. 2003;52:1-33. Ott MJ and Aruda M. J Pediatr Health Care. 1999;13:211-216. Ribeiro RM, et al. Microbes and Infection. 2002;4:829-835.
Modes of Transmission
Transfusion (blood, blood products) Fluids (blood, semen) Tattoos; Body piercing Mother to infant
Hepatitis B
Child to child
Icteric phase: liver damage: jaundice, dark urine, pale stools Recovery: decline in fever; renewed appetite
FASE REACTIVATION
FASE REACTIVATION
Rekomendation to treat
FASE REACTIVATION
FASE REACTIVATION
Rekomendation to treat
41
HBV DIAGNOSIS
CLINICALL LABORATORY Liver enzymes Serology HBeAg, HBcAg, virus: active infection Anti-HBc IgM: acute active infection Anti-HBe IgG: acute infection
Healthy Liver
Hepatic Fibrosis
Cirrhosis
Liver Cancer
Healthy Liver
Hepatic Fibrosis
Cirrhosis
Liver Cancer
HBV Complications
Chronic HBsAg antigenemia
Hepatocellular carcinoma
MANAGEMENT HBV
PREVENTION OF LIVER CIRRHOSIS,HEPATOMA AND MORTALITY
MANAGEMENT
--1. Evaluation of the disease 2. Non-specific/specific therapy 3. Monitoring and surveillance The diagnosis of CHB infection HBsAg at least 6 month HBeAg and Anti-HBe Viral replication and thus infectivity. ALT/AST measured inflammation Liver Biopsy is more accurate USG/Fibro Scan parenchymal impairment, fibrosis Early cirrhosis ussually not detected by ultrasound
MANAGEMENT
Non-spesific advice General advice
CHB infection potentially infectious should not share toothbrushes or shaving equipment Household contacts and sexual partners should have their hepatitis serology determined and should be immunized if found negative for HBsAg, anti-HBs and anti HBc When a woman becomes pregnant inform her gynecologist about her HBV status appropriate steps can be taken to immunize her baby at birth A Baby born to HBeAg-positive mother should be given hepatitis B immune-globulin at the same time
MANAGEMENT
Diet
Nutritious diet to maintain normal body weight May be needed protein, salt and water restriction
Exercise Subjects with asymptomatic infection should continue their regular form of exercise With cirrhosis should avoid strenuous jogging and heavy weight lifting
MANAGEMENT
Alcohol and Drugs Should be avoided Potentially hepatotoxic agents or regular alcohol intake, steroids and immunosuppressive agents In Endemic countries patients need steroids or immunosuppressive drugs,HBV status checked to prevent HBV flares.
56
HBeAg
ALT Other
HBeAg+
Normal --
HBeAg+
High or fluctuating Active inflammation on liver biopsy Yes
No
Pemberian terapi imunomodulator atau nucleoside analog b ergantung kepada : 1. Genotipe HBV 2. Kadar ALT 3. Kadar serum HBV DNA 4. Sirosis kompensasi atau dekompensasi 5. Resistensi Obat 6. Cost effective
Yun FL et al Liver Int 2005;25:472 Yun FL.et al Guidelines for HBV management, APASL 2008
62
Rekomendasi terapi dari EASL (European Association for the Study of the Liver) 2009
Indikasi terapi sama untuk pasien HBeAg (+) dan HBeAg (-). Memenuhi 3 kriteria : kadar serum HBV DNA, kadar serum aminotransferase & grade/tingkat histologi. Pasien dapat diterapi bila kadar HBV DNA > 2000 IU/ml (10.000 kopi/ml) dan atau kadar ALT diatas BANN, dan biopsi hati menunjukkan moderate sampai severe necroinflammation dan atau fibrosis memakai sistim skor standar (contoh paling sedikit grade A2 atau tingkat F2 skor METAVIR.
63
ALT <BANN
ALT >BANN
>2X
Dekompensasi hati
Ya
AN
Respoms Tidak Respons MONITORING Strategi lain??? Kombinasi IFN dan AN Kombinasi AN Terapi alternatif
HBV Prevention
Screen blood products Sterilization of needles, etc. Avoiding intimate contact, e.g., household or sexual contacts Vaccination
HEPATITIS C
Introduction
Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide The long-term hepatic impact of HCV infection is highly variable, from minimal changes to chronic hepatitis, extensive fibrosis, and cirrhosis with or without hepatocellular carcinoma (HCC)
Prior to the 1990s, the principal routes of HCV infection were via blood transfusion, unsafe injection procedures, and intravenous drug use.
Introduction
Currently, new HCV infections are primarily due to intravenous or nasal drug use, and to a lesser degree to unsafe medical or surgical procedures. Parenteral transmission via tattooing or acupuncture with unsafe materials is also implicated in occasional transmissions.
Liver cirrhosis
End-stage liver disease HCC
10
30
40
Population at Risk
Transfusion of blood products before 1992 Intravenous drug use Nasal inhalation of cocaine Chronic renal failure on dialysis Incarceration Occupational exposure to blood products Transplantation of an organ/tissue graft from
Centers for Disease Control and Prevention. Hepatitis C fact sheet. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/c/fact.htm. Accessed February 1, 2006.
antiHCV
HCV RNA
Titer
ALT
HCV Counseling
Do not donate blood, body organs, other tissue or semen Do not share items that might have blood on them
personal care (e.g., razor, toothbrush) home therapy (e.g., needles)
HCV Counseling
HCV Diagnosis
Most patients asymptomatic Abnormal liver function tests; AST/ALT Hepatitis C antibody (EIA) RIBA HCV RNA levels Liver biopsy: grade and stage damage
Diagnosis Hepatitis C
Kelompok resiko tinggi / terpapar darah yang diduga terkontaminasi HCV: skrining Anti-HCV
Anti-HCV positif
Quantitative assays
Detection cutoff > qualitative
Jika positif
Hepatitis C Kronik
1. Anti-HCV positif > 6 bulan 2. HCV RNA positif 3. ALT meningkat / normal
Gejala & tanda biasanya ringan / tidak khas (asimtomatik) Singkirkan penyebab lain (virus, obat, autoimunitas) Pikirkan kemungkinan infeksi ganda (dgn HAV/HBV/HIV) Periksa genotipe HCV lama pemberian terapi IFN
1. NIH Consensus Statement Online. Management of hepatitis C 2. British Liver Trust Information Service. A guide to liver function tests 3. Canadian Liver Foundation. (www.liver.ca/Liver_Disease/How_is_Liver_Disease_Diagnosed/Liver_Biospy.aspx)
Purpose
Confirm viremia. Assess liver function. Assess for iron overload. Detect autoimmune hepatitis. Detect 1- antitrypsin deficiency.
The general management of patients with chronic hepatitis C is similar to that for chronic hepatitis B infection. Alcohol should be avoided as this has been shown to accelerate liver damage. Reducing the number of patients with HCV viraemia : 1. Screening of blood donors for anti-HCV 2. Active treatment of viraemic patients with Interferon and/or Ribavirin
HCV Therapy
Pegylated Interferon injections weekly AND Ribavirin pills (or liquid) twice daily
HEPATITIS FULMINANT
HEPATITIS FULMINANT
Hepatic failure with in 2-3 weeks. Reactivation of chronic or acute hepatitis Massive necrosis, shrinkage, wrinkled Collapsed reticulin network Only portal tracts visible Little or massive inflammation More than a week regenerative activity Complete recovery or - cirrhosis.
ACUTE LIVER FAILURE, acute liver disease with clinically jaundice to encephalopathy progresive rapidly FULMINANT HEPATIC FAILURE, acute liver failure with hepatic encephalopathy,develoving less than 2 weeks or 8 weeks after onset jaundice
SUBFULMINANT HEPATIC FAILURE, acute liver disease with hepatic encepalopathy,develoving from 2/8 weeks to 3/6 month onset jaundice
OGRADY dkk :
Based liver failure, onset of jaundice, encepalopathy HYPERACUTE LIVER FAILURE,interval less than 7 days ACUTE LIVER FAILURE,interval 8 and 28 days SUBACUTE LIVER FAILURE,interval between 5 and 12 weeks
Clinical features
ICKTERUS PROGRESIF BILIRUBIN > 20mg % NAUSEA,MALAISE,VOMITING,FEVER.LIVER SIZE SMALL.COMA MAY RAPIDLY (FEWDAYS). TACHYCARDIA,HYPOTENSION,HYPERVENTILAT ION ,CEREBERAL OEDEME ARE LATER FEATURES
ETIOLOGI
VIRAL HEMORAGIC FEVER VIRUS HEPATITIS VIRUS SITOMEGALOVIRUS HEPATITIS A HERPES SIMPLEX VIRUS HEPATITIS B EPSTEIN BARR VIRUS HEPATITIS C PARAMIXOVIRUS HEPATITS E ADENOVIRUS HEPATITIS G DRUG/ TOXIN, HALOTHANE ISCHEMIC ACETAMINOFEN ISCHEMIC HEPATITIS ISONIAZID-RIFAMPICIN SURGICAL SHOCK ANTIDEPRESANT ACUTE BUCCHIARY SYNDROME NSAID VALPROIC ACID MISCELLANEUS (RARE) MUSHROOM POISONING HEAT STROKR HERBAL REMEDIES SEVERE BACTERIAL INFECTION AMANITA POISONING MASSIVE MALIGNANT INFILT. YELLOW PHOSPORUS BACILLUS CEREUS EMETIC TOXIN
MANAGEMENT
FARMAKOLOGI
N-ASETIL SISTEIN
PROSTAGLANDIN HAEMOPERFUSI ARANG KOLOUMN HEPATOSIT
MOLEKULER
REGULASI SITOKIN REGULASI KASKADE KOAGULASI INHIBISI APOPTOSIS HEPATOSIT GROWTH FACTOR
HEPATOSIT TRANSPLANT
TRANSPLANTASI LIVER TRANSPLANT
HEPATITIS D
HEPATITIS AKUT - D
Terdeteksi bersamaan dengan virus Hepatitis B. Prevalensi HDV (+) berhubungan dengan
prevalensi infeksi HBV (+). HDV lebih dominan didaerah tropikal dan subtropik,di negara berkembang drpd negara maju (Barat).
Gold standard d/: HDV RNA (+) atau HDAg (+) liver.
Clinical finding, acute HBV-HDV coinfection, severe hepatitis withhepatocelluler necrosis and inflammation,Chronic. Chronic HBV-HDV infection,initial severe liver disesase,may be chronic healthy carrier state similar with HBV chronic
Diagnosa , Anti HDV (+) IgM /IgG,in the presence Hepatitis B patient Therapi ,is problematic, initial Interferron alpha result in clinical and biochemical respons,but relaps are common Prevention,dvaccination with Hepatitis B Vaccine
HEPATITIS E
HEPATITIS E
Nonenveloped spherical RNA virus Transmission fecal oral,main target hepatocyte Endemic in India,Southeast and Central Asia The largest affected in young adult (15-40 years) Incubation period 2 10 weeks Clinical same with HepatitisA,but generrally more severe Diagnosed presence anti HEV (+) / IgG or IgM,HEV RNA (+)
TREAEMENT,supportive and no effective vaccine available Prvention,improved sanitation,sanitary handling,food,water, boil of water
HEPATITIS G
HEPATITIS G
Termasuk Flava virus.
Terdistribusi secara luas. Ditularkan melalui parenteral, seksual dan perinatal. HGV RNA dideteksi dengan PCR. HGV tidak mempengaruhi respon untuk terapi antiviral.
DILD
Many drugs including herbal products can cause acute hepatotoxicity will induce chronic hepatitis with prolonged administration. These include gold, isoniazid, ketoconazole, methyldopa, nitrofuratoin, phenylbutazone and silfonamides. Oxyphenisatin the first agent known to be associated with chronic hepatitis. Older females are affected more frequently.
It is important to exclude wilsons disease as a cause of chronic hepatitis when it apprears in patients younger than 35 years. Liver disease often precedes symptoms attributed to central nervous system involvement and the appearance of Kayser-Fleischer rings and may be the initial presentation in 50 % of cases. Elevated urinary and hepatic copper levels are diagnostic. Improvement may be achieved by early treatment with D-penicillamine.
Wilsons disease