Farmakoterapi

Viral Hepatitis

Martanty Aditya

Universitas Ma Chung, 2017

 Virus Hepatitis

Hepatitis A
International travelers to endemic areas (e.g., Africa, Asia, and parts of South America)
Sexual contact with infected persons (e.g., men having sex with other men)
Shellfish infected with HAV (e.g., raw oysters)
Day care centers or household contacts with people infected with HAV
Health care workers
Intravenous drug users using unsterilized needles
Workers involved with non-human primates Food service handlers
Patients with clotting factor disorders
Individuals residing in health care institutions

Hepatitis B and Hepatitis D

Men having sex with other men
Individuals with multiple heterosexual partners
Intravenous drug users using unsterilized needles
Recipients of blood products
Household contacts with acute hepatitis B with open cuts
Health care providers in contact with contaminated needles
Patients undergoing dialysis

Hepatitis C
Recipients of blood products
Health care providers in contact with infected needles
Individuals having multiple sexual partners
Perinatal transmission (less than 5%)
Unprofessional body piercing and tattooing

Hepatitis E
International travelers to endemic areas (e.g., parts of Asia, Africa, and Mexico)
Ingesting foods and drinks contaminated with bodily waste

Virus hepatitis terdiri atas 5 tipe dimana ada yang bersifat akut maupun kronik yang didasarkan pada
lama penyakit. Hepatitis akut dihubungkan dengan 5 tipe virus namun tidak semuanya berkembang
menjadi kronis atau lebih dari 6 bulan. Hepatitis kronis dihubungan dengan virus B, C dan D. virus
hepatitis dapat berkembang menjadi sirosis yang dapat menginduksi end-stage liver disease (ESLD).
Komplikasi yang ditimbulkan oleh ESLD adalah edema, asites, jaundice, ensefalopati hepatik, infeksi
dan perdarahan varises esofageal. Hal ini yang menyebabkan mengapa hepatitis kronis perlu diterapi
untuk mencegah terjadinya ESLD.

Gejala umum virus hepatitis

Awalnya kebanyakan pasien yang terinfeksi dengan virus tidak memiliki gejala. Namun ada pula yang
 CHAPTER 21 / VIRAL HEPATITIS 351

memiliki
or intramuscular gejalaadministration,
(IGIM) diantaranya adanya
but onlygejala
IGIMseperti
is flu,
Thedemam,
risk of kelelahan/rasa
infection may be tidak enak badan,
decreased by 90% if IGIM is
used for prevention of hepatitis A. IGIM does not confer life- given within 2 weeks of being exposed to the hepatitis A virus.
anoreksia,
long immunity, but it mual, muntah,
is effective in diare, urin berwarna
providing gelap, gatal
pre-exposure IGIMdanmaynyeristill
perut.
be beneficial if it is given more than 2 weeks
5
and postexposure prophylaxis against HAV. after exposure
Tanda lainnya adalah jaundice dengan adanya bintik putih pada mata (icterus to a known caseatau
sclera) of HAV,
kulit,asadanya
it may decrease the
Adverse effects of IGIM are rare. There have been reports of severity of hepatic damage.1,5
anaphylaxis hepatomegaly
in individuals danwhosplenomegaly serta hepatik
have immunoglobulin ensefalopati ditandai dengan koma.
A defi-
ciency after receiving repeated IG administration. Therefore, Hepatitis A Vaccine
these patients should not receive IGIM. IGIM is not con- Persons at risk of acquiring the HAV should receive the hepa-
traindicatedHepatitis
in pregnantAor lactating women or infants requir- titis A vaccine when appropriate.
ing hepatitis A immunization. The thimerosal-free preparation There is no benefit in administering the vaccine after a per-
Epidemiologi
should be used in infants.1 dan Etiologi son has been exposed to the HAV. Two inactivated hepatitis A
IGIM should be injected
Prevalensi intoyaitu
tertinggi a deltoid
padaornegara
glutealkurang
muscle.berkembang
It termasuk
vaccines, Havrix afrika
and dan
VAQTA,America selatan,intimur
are available the United States
does not affect the immune response of inactivated vaccines, and are effective in providing active immunization. The major
tengah
oral polio virus, dan asia
or yellow tenggara
fever vaccine.sedangkan di negara of
The administration maju seperti Australia,
difference eropathe
between utara,
twojepang danisamerika
vaccines that HAVRIX con-
live vaccines [e.g., measles, mumps, rubella (MMR) vaccine] tains 2-phenoxyethanol as a preservative whereas VAQTA is
prevalensiny rendah, hal ini disebabkan karena adanya program vaksin. Sebanyak 31% populasi
concomitantly with IGIM may decrease the immune response preservative-free.1 Either vaccine is effective in providing
significantly;Amerika terinfeksi
thus, MMR andHIV dan seluruh
varicella vaccine Meksiko
shouldAmerika
be memiliki risiko yang lebih
active pre-exposure besar mengalami
prophylaxis when givenHAV in two injections
delayed for at least 3 and 5 months, respectively, after IGIM 6 months apart (referred to as months 0 and 6). The two vac-
dan Amerika Additionally,
has been administered. Afrika lebih mudah
IGIM terinfeksi
should notdibandingkan
be Kaukasian. HAV terdeteksi pada feses yang
cines are considered interchangeable, and doses are dependent
given withinterkontaminasi
2 weeks of thedan MMR administration
orang yang terinfeksior within
melalui rute onoral-fekal.
age (Table Wabah
21–3).terutama terjadi lingkungan
3 weeks of the varicella vaccine to maximize the efficacy of the Efficacy is defined by measuring antibody response. For
immunization.dengan
1 sanitasi yang kotor. Sampai saat ini HAV jarang dihubungkan dengan kondisi kronis dimana
HAVRIX, levels greater than 20 mIU/mL measured with the
manifest terbanyak dihubungkan dengan hepatitis fulminant dimanaimmunoassay,
modified enzyme rata-rata 1:100 mengalami
and for VAQTA, levels greater
Pre-exposure Prophylaxis than 10 mIU/mL measured with the modified radioimmuno-
kematian.
Pre-exposure prophylaxis with IGIM is indicated for individ- assay are considered protective. After the first dose of vaccine has
uals at high risk of acquiring the HAV who cannot receive the been administered, 94% to 100% of adults and 97% to 100% of
hepatitis A vaccine (e.g., because of allergy to the components children and adolescents develop protective antibody concentra-
Patofisiologi Additionally, travelers who plan
alum or 2-phenoxyethanol). tions against the HAV. All recipients over the 2 years of age receiv-
to depart forHepatitis
endemicA areas within 2 weeks and have not yet
adalah sebuah RNA untai tunggal tidak terlapisiing the diklasifikasikan
second dose at month
sebagai6 genhavehepatovirus
100% antibody coverage,
received the hepatitis A vaccine should receive IGIM because therefore, postvaccination CHAPTER
measurement21 / ofVIRAL HEPATITIS
antibody 349
response is
dari keluarga Picornaviridae. Satu-satunya
active vaccine immunity takes several weeks to develop. host HAV adalah manusia
not required. 1 dengan sel hepar sebagai tempat

The dose of the IGIM determines the duration of coverage. The hepatitis A vaccine may provide effective immunity
untuk
TABLE replikasi
21–2. virus. Proses
Interpretation degradasi
Hepatitisvirus, HAV dilepaskan masuk ke dalam sistem bilier
A dose of 0.02 mL/kg confers immunity of Viral
against hepatitis ASerology
for Panels
for 8 years in adults and children. Additionally, kinetic models
menyebabkan
less than 3 months
Type
peningkatan
and doses konsentrasi
of 0.06 mL/kg virus
provide
Laboratory Test
diResult
immu- feses. have theorized that immunity with the vaccine may be
Interpretation of Panel
nity up to 5 months. If protection against HAV is required longer than 20 years, but this has not been confirmed in clin-
Hepatitisthen
beyond 5 months, A IgM anti-HAV
readministration of IGIM may Negative
be ical trials.1 Susceptible to infection
1,5 IgG anti-HAV Negative
indicated. The most common adverse effects in adults include injec-
IgM anti-HAV Positive tion site reactions
Acutely infected
(e.g., tenderness, pain, and warmth),
Postexposure Prophylaxis IgG anti-HAV Positive headaches within
Immune 5 due
daystoafter vaccination,
either and fatigue. Local
natural infection
Individuals in contact with people infected with acute HAV, reactions may be or HAV vaccine by using an appropriate needle
minimized
Diagnosa
including household hepatitis
a
Hepatitis Band sexualApartners,
ditandai dengan
HBsAg staff and adanya kadar length
Negative
children IgM anti-HAV onyang
basedSusceptiblemuncul setelah
to infection
the person’s age 3 and
and size minggu
by administering
anti-HBc
from day care facilities, and food handlers of restaurant estab- Negative the injection intramuscularly in the deltoid muscle. Children
terpapar dan tidak terdeteksi lagi sampai dengan
anti-HBs 6 bulan. Sebaliknya apabila nilai IgM dan IgG anti
Negative
lishments may be candidates for postexposure prophylaxis. may also have feeding disturbances. Hepatitis A vaccine given
HAV positif menandakanHBsAg
anti-HBc
Negative
adanya proteksi dan sistem
Positive
Immune due to natural infection
imun bawaan melawan hepatitis A
anti-HBs Positive
TABLE 21–3. Recommended
HBsAgIntramuscular Doses of Hepatitis A Vaccines
Negative Immune due to hepatitis B vaccination
anti-HBc Negative
Recipient
anti-HBsAge Positive No. of Schedule
Product (Years) Dose Volume (mL) Doses (Months)
HBsAg Positive Acutely infected
VAQTA 1–18
anti-HBc 25 units
Positive 0.5 2 0, 6–18
Greater than
IgMoranti-HBc
equal to 19 50 units
Positive 1 2 0, 6
Havrix 1–18
anti-HBs 720 EL units
Negative 0.5 2 0, 6–12
Greater than or equal to 19
HBsAg 1440 EL units
Positive 1
Chronically 2
infected 0, 6–12
anti-HBc
EL units, enzyme-linked immunosorbent assay units.Positive
IgMPharmacotherapy
From Chan J. Viral hepatitis. anti-HBc Negative Program. 5th ed. Kansas City: MO, American College
Self-Assessment
anti-HBs
of Clinical Pharmacy, 2005:1, 4, with permission. Negative
HBsAg Negative Four interpretations possibleb
anti-HBc Positive
anti-HBs Negative
Hepatitis C anti-HCV Negative Susceptible to infection
anti-HCV Positive Acutely or chronically infected
Hepatitis Dc IgM anti-HDV Positive Acute HBV-HDV coinfection
HDVAg Positive
HBsAg Positive
HBeAg Positive
Terapi
Immunoglobulin digunakan untuk pencegahan sebelum dan setelah terpaparHAV. Sediaan steril
mengandung antibody. Dosis yang digunakan untuk profilaksis jangka pendek <3 bulan menggunkana
single dose 0.02ml/kg BB diberikan secara im. Sedangkan untuk jangka panjang 5 bulan dengan dosis
0.06ml/kg BB

Hepatitis B
Epidmiologi dan etiologi
Hepatitis B terinfeksi melalui darah dan menulari hampir 2 miliar orang di dunia. Rata-rata 350 juta
orang mengalami infeksi kronis dan menyebabkan terjadinya sirosis dan komplikasi ESLD. Kematian
yang dihubungkan dengan hepatitis B berkisar antara 500.000-750.000/tahun. Meskipun telah terdapat
vaksin yang efektif terhadap HBV namun lebih dari 300.000 orang dengan diagnosa baru setiap
tahunnya. Prevalensi hepatitis B kronis bergantung pada daerahnya dimana peningkatan laju pada
Amerika Utara 1% dan Eropa Barat dibandingkan 10-15% pada Asia Tenggara. Konsentrasi tertinggi
ditemukan di darah dan cairan serosa. Hal ini yang menyebabkan penularan utama hepatitis B melalui
darah atau cairan tubuh melalui perinatal, seksual atau paparan perkutan. Bayi dengan ibu yang
terinfeksi HBV secara aktif akan bereplikasi dan memiliki risiko 90% berkembang menjadi hepatitis
kronis B, sedangkan bayi yang lahir pada daerah endemic tidak akan terinfeksi, dan risiko terkena 30-
60% setelah 5 tahun dengan transmisi horizontal.

Patofisiologi
Hepatitis B atau yang lebih diketahui Dane particle berasal dari keluarga Hepadnaviridae. HBV
merupakan susunan yang unik terdiri dari DNA untai ganda dengan lapisan fosfolipid mengandung
hepatitis B surface antigen (HBsAg) dikelilingi nukleokapsida. Nukleokapsida mengandung protein
inti yang menghasilkan hepatitis B core antigen (HBcAg) yang tidak dapat diketahui dalam serum.
Mekanisme yang benar dari kerusakan hepatoseluler karena hepatitis B masih belum diketahui dengan
pasti. Namun sampai saat ini diketahui karena adanya reaksi imun sitotoksik terjadi ketika HBcAg
diekspresikan ke permukaan sel hepatic. Untungnya antibody melawan hepatitis B core antigen (anti-
HBc) terukur di dalam darah, dimana anti-HBc melalui IgM mengindikasikan infeksi aktif dan anti-HBc
menjadi IgG dihubungkan dengan infeksi kronis atau sistem imun melawan HBV.
Replikasi virus terjadi ketika hepatitis B envelope antigen (HBeAg) diketahui keberadaannya di dalam
darah. DNA HBV dimanfaatkan untuk mengukur inefektivitas virus dan menilai atau mengukur replikasi
virus. Sekali infeksi hepatitis B dihancurkan, antibody melawan hepatitis B envelope (anti-HBe) dan
antibody melawan hepatitis B surface antigen (anti-HBs) sampai kadar HBV DNA tidak terdeteksi.
 Type Laboratory Test Result Interpretation of Panel
during Hepatitis
pregnancyA has not been IgM anti-HAV
evaluated Negative protection against
in clinical trials. Susceptible
acquiringtotheinfection
HBV when the immunization is
Since both brands of vaccine are made IgG anti-HAV
from inactivated HAV, Negative given at months 0, 1, and 6. The two non-dialysis formulations
the risk of developing fetal complicationsIgM anti-HAVshould be minimal. Positive of the hepatitisAcutely infected
B vaccines are considered interchangeable, but
IgG anti-HAV Positive
the same brand should be used for the entire three-dose series.
Immune due to either natural infection
Hepatitis B Prevention Additionally, the doses depend on the person’s age (Table 21–4).
or HAV vaccine
❹ Individuals may
a minimize their risk of acquiring the hepa- The difference between the two vaccines is that Engerix-B con-
Hepatitis B HBsAg Negative Susceptible to infection
titis B infection by avoiding contaminated tains trace amounts of thimerosal that is not used as a preser-
anti-HBc blood productsNegative or
indulging in high-risk behavior suchanti-HBsas intravenous drug use.NegativeIn vative but is produced during the manufacturing process;
addition, those who are at high HBsAg risk of acquiring the HBV Recombivax HB is completely free of thimerosal.
Negative Immune due to natural infection
(Table 21–1) should be vaccinated with the hepatitis B vaccine. 8 For optimal response, the hepatitis B vaccine should be
anti-HBc Positive
In some cases, postexposure prophylaxis anti-HBs with hepatitisPositive B administered intramuscularly only (into the anterolateral
immune globulin (HBIG) may be recommended to prevent the thigh region in neonates and infants; the deltoid region in
HBsAg Negative Immune due to hepatitis B vaccination
development of acute infection and complications associated adults) and not intravenously or intradermally. The vaccine
anti-HBc Negative
with HBV. anti-HBs Positive should not be given in the gluteal region, as it may result in
lower rates of immunity. In rare cases, the vaccine may be given
HBsAg Positive Acutely infected
Hepatitis B Immune Globulin anti-HBc subcutaneously in individuals at risk for hemorrhage (e.g.,
Positive
Hepatitis B immune globulin (HBIG) IgM isanti-HBc
a sterile solution con-
Positive
hemophiliacs); however, this route of administration should be
taining antibodies prepared from anti-HBs pooled human plasma that Negative used with caution, as subcutaneous nodules have developed
has a high concentration of anti-HBs (antibodies to hepatitis when other similar vaccines have been used.8
HBsAg Positive Chronically infected
B surface antigen). HBIG providesanti-HBc passive immunization Positive for The efficacy of the hepatitis B vaccine is established when
postexposure prophylaxis against IgM the HBV.
anti-HBcSimilar to IGIM, Negative antibody concentrations are greater than 10 mIU/mL. After
HBIG should only be administered intramuscularly.
anti-HBs Negative completing the vaccination series given at months 0, 1, and 6,
The most common side effectsHBsAg of HBIG include erythema 96% of recipients obtain adequate antibodyblevels; for this rea-
Negative Four interpretations possible
at the injection site, headaches, anti-HBc myalgia, fatigue, urticaria, Positive son, postvaccination testing is not usually recommended.
nausea, and vomiting. Serious adverse effects are rare and may
anti-HBs Negative However, protective antibody levels may be decreased in
includebHepatitis
liver function test abnormalities, arthralgias, and ana- immunocompromised patients (e.g., human immunodeficiency
(1) May beC recovering from anti-HCV
acute HBV infection; (2) Negative
May be distantly immune Susceptible
and test to isinfection
not sensitive enough to
phylactic reactions. HBIG should be used with caution in virus (HIV)-positive, hemodialysis, or immunosuppressive
detect very low level of anti-HBs anti-HCVin serum; (3) May be susceptible withAcutely
Positive a false-positive
or anti-HBc;
chronically (4) May be
infected
individuals who have
undetectable experienced hypersensitivity reactions therapy); postvaccine testing may be warranted 1 to 6 months
c level of HBsAg present in the serum and the person is actually a carrier.
Hepatitis D IgM anti-HDV
to immune globulin or those who have immunoglobulin A Positive Acute HBV-HDV coinfection
after completing the vaccination series in these patients.8 The
deficiency. Similar to IGIM, concomitant HDVAg administrationPositive of duration of immunity and whether a booster dose of the hepa-
Hepatitis B terdiagnosa HBsAg ketika HBsAg terdeteksi dalamtitisserum.
Positive Nukleopsida
B vaccine is required aredaristill
HBsAg mengandung
being investigated.
HBIG and live vaccines should be avoided because the efficacy
HBeAg 8 Positive The most frequent adverse effects are localmenjadi
reactions at the
protein inti yang
of the immunization may menghasilkan
decreaseanti-HBc HBcAg yang tidak
significantly. terdeteksi
Positive dalam serum. Adanya anti-HBc
injection site (pain, tenderness, erythema, swelling, and pruri-
Hepatitis
IgM
Hepatitis E
mengindikasikan
B Vaccine IgM anti-HEV
infeksi akut, dan anti-HBc Negative
menjadi
tus),IgG Susceptible
dihubungkan
fevers (greater to infection
dengan
than 37.5°C or infeksi
99.5°F), kronis atau
headaches, dizziness,
The two hepatitis B vaccines available IgG inanti-HEV
the United States Negative
are and irritability. Anaphylaxis and hypersensitivity reactions have
sistemHBimun
Recombivax and melawan
Engerix-B.HBV.IgM Replikasi
These anti-HEV
vaccines are virus dtandai dengan
Positive
produced been adanya
reported kadar
Acutely
rarely HBeAg
and occuryang
infected withindigunakan
a few hoursuntuk
after vaccine
with recombinant DNA technology IgGbyanti-HEV
inserting the gene Positive
for administration.Immune due to natural
In rare instances, a serum infection
sickness–like apparent
HBsAgmengukur inefektivitas
into the plasmid
a
virus danbymenilai
that is synthesized replikasi virus.
Saccharomyces Saat infeksi
hypersensitivity hepatitis(arthralgia,
syndrome B dihancurkan
urticaria,maka
ecchymoses,
Centers for Disease Control and Prevention. Hepatology. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/
cerevisiae cells.
terjadi ❺ Both
peningkatan
Bserology.htm.
vaccines
Accessedkadar are effective
anti-HBe
February
in providing erythema multiforme,
dan anti-HBs dan nilai HBV DNA menjadi tidak terdeteksi.
19, 2006.
and erythema nodosum) has been
b
(1) May be recovering from acute HBV infection; (2) May be distantly immune and test is not sensitive enough to detect
very
TABLElow21–4.
level Recommended
of anti-HBs in serum; (3) May be
Intramuscular susceptible
Dosing withfor
Regimens a false-positive anti-HBc; (4) May be undetectable level
Hepatitis B Vaccines
of HBsAg present in the serum and the person is actually a carrier.
c
Hepatitis D should be suspected in those who have HBsAg positivity.
Patient DoseHepatitis D may present as No.
either
of coinfection where
Schedule
both HDV and HBV serologies appear
Product simultaneously whereas for(mcg)
Categories superinfection, HBV
Volume has been
(mL) present for (months)
Doses some time,
and later HDV develops.
Recombivax
anti-HAV, HB
hepatitis A antibody; 0–19 years of
anti-HBc, age
hepatitis B core antibody; 5 anti-HBs, 0.5 3 antibody;
hepatitis B surface 0, 1, 6
HBsAg,
a
11–15hepatitis
hepatitis B surface antigen; anti-HCV, C antibody; anti-HDV,10
years of age 1
hepatitis D antibody; 2 hepatitis E1,antibody;
anti-HEV, 4–6
HAV, hepatitis A virus;Greater than or equal
HBV, hepatitis to 20
B virus; years
HDV, of age D virus;
hepatitis 10HDVAg, hepatitis
1 D antigen;3IgG, immunoglobulin
0, 1, 6
G; IgM, immunoglobulin M. Hemodialysis 40 1 3 0, 1, 6
Engerix-B 0–19 years of age 10 0.5 3 0, 1, 6
Greater than or equal to 20 years of age 20 1 3 0, 1, 6
Hemodialysis 40b 2 4 0, 1, 2, 6
a
Adolescents 11 through 15 years of age may receive either the 5 mcg, 3-dose pediatric formulation or a 10 mcg, 2-dose regimen
using the adult formulation.
b
Two × 20 mcg in one or two injections.
From Chan J. Viral hepatitis. Pharmacotherapy Self-Assessment Program. 5th ed. Kansas City: MO, American College of Clinical
Pharmacy, 2005:1, 8, with permission.
 HBeAg status Treat: adefovir, entecavir, or
PEG IFN-α2a

Positive Negative: 1. Monitor for increases in serum ALT

2. Consider biopsy if HBV DNA levels >2,000 international units/mL
Terapi
Algoritma terapi hepatitis kronis B
<20,000 international units/mL Monitor
HBV DNA levels

ALT levels ≥20,000 international units/mL Consider liver biopsy

Normal Elevated
Treat if known histologic
treatment algorithm for disease
infection based on the
American Gastroentero-
alanine transaminases; HBeAg status
a Therapy Treat: adefovir, entecavir, or
shouldbe considered in all patients with known histologic disease regardless
gen; PEG INF, pegylated PEG IFN-α
of HBV DNA levels, ALT levels, or HBeAg status.2a
m reference 29.)

PROACH TO TREATMENT
Positive Negative: ■ NONPHARMACOLOGIC
1. Monitor for increases in serum ALT THERAPY
2. Consider biopsy if HBV DNA levels >2,000 international units/mL
s monitored by biochemical (normalization All chronic HBV patients should be counseled on preventing disease
c examination of liver cells from biopsy (a transmission. Sexual and household contacts should be vaccinated.
ease in histology activity compared to base- To minimize
<20,000further liverunits/mL
international damage, all chronic
MonitorHBV patients should
ic response (undetectable serum HBV DNA avoid alcohol and be immunized against HAV. No level of alcohol
HBV DNA levels
in HBeAg-positive patients).27 Maintenance use has been established as safe.29 Moreover, patients are encour-
efined as durability of response. In HBeAg- aged to≥20,000
consultinternational units/mL provider
their medical Consider
beforeliverusing
biopsyany new
sful therapy includes loss of HBeAg status medications, including herbals and nonprescription drugs.21
anti-HBeAg. Other serologic markers are Herbal medicines are an intriguing option to many patients.
n clinical trials. Recommendations for treat- Four common preparations include TreatPhyllanthus, milk thistle, gly-
if known histologic
nt’s age, serum
reatment HBVforDNA and ALT levels, as
algorithm cyrrhizin (licorice root extract), and a mixture disease of herbs known as
ce and clinical
nfection based on progression
the of disease (Figs. Liv 52. Although some of the products may have some benefits, the
l chronicGastroentero-
merican HBV patients are candidates for methodologic qualities of the trials evaluating the herbs are poor.
s may be
alanine best managed with
transaminases; periodic
a Therapy moni- Randomized,
should be considered placebo-controlled
in all patients studies
with known histologic diseaseand long-term followup
regardless
n; PEG because
ession INF, pegylated
the chancesof for
HBVtherapeutic data or
DNA levels, ALT levels, areHBlacking. Meta-analysis of existing studies demonstrated
eAg status.
reference
and do not29.)outweigh the risks and costs that milk thistle and Liv 52 do not affect the course of liver disease.
nt. Various guidelines have been published Herbal treatment is not recommended for patients with chronic
ore drugs are indicated for use in HBV.27,29,38 hepatitis B.39
Algoritma terapi hepatitis
ROACH TO TREATMENT kronis B dengan sirosis
■ NONPHARMACOLOGIC THERAPY
monitored by biochemical (normalization All chronic HBV patients should be counseled on preventing disease
examination of liver cells from biopsy (a Compensated cirrhosis Sexual and household
transmission. Decompensated cirrhosis
contacts should be vaccinated.
se in histology activity compared to base- To minimize further liver damage, all chronic HBV patients should
response (undetectable serum HBV DNA avoid alcohol and be immunized against HAV. No level of alcohol
n HBeAg-positive patients).27 Maintenance HBV has been established as safe.29 Moreover,
use DNA 1. Waitingpatients aretransplant
list for liver encour-
ined as durability of response. In HBeAg- aged to consult their medical provider before
2. Treat: using any new
ul therapy includes loss of HBeAg status medications, including herbals and nonprescription drugs.+21adefovir
a. Lamivudine
nti-HBeAg. Other serologic markers are Herbal medicines are an intriguing optionorto many patients.
<2000 international units/mL ≥2000 international units/mL b. Entecavir + adefovir
clinical trials. Recommendations for treat- Four common preparations include Phyllanthus, milk thistle, gly-
’streatment
age, serum HBV
algorithmDNA and ALT levels, as cyrrhizin (licorice root extract), and a mixture of herbs known as
e and clinical progression
dations of the Ameri- of disease (Figs. Liv 52. Although some of the products may have some benefits, the
chronic HBV
ssociation patients are candidates Observe
for chronic for methodologic qualities of the trials evaluating the herbs are poor.
may
atients with cirrhosis. with periodic moni-
be best managed Randomized, placebo-controlled studies and long-term followup
or Treat with adefovir or entecavir
29.) because the chances for therapeutic
ssion data are lacking. Meta-analysis of existing studies demonstrated
d do not outweigh the risks and costs that milk thistle and Liv 52 do not affect the course of liver disease.
. Various guidelines have been published Herbal treatment is not recommended for patients with chronic
e drugs are indicated for use in HBV.27,29,38 hepatitis B.39

Compensated cirrhosis Decompensated cirrhosis

HBV DNA 1. Waiting list for liver transplant

2. Treat:
a. Lamivudine + adefovir
or
<2000 international units/mL ≥2000 international units/mL b. Entecavir + adefovir

reatment algorithm
tions of the Ameri-
Observe
ociation for chronic
tients with cirrhosis.
or Treat with adefovir or entecavir
9.)
354 SECTION 3 / GASTROINTESTINAL DISORDERS

TABLE 21–6. Recommendations for Hepatitis B Prophylaxis to Prevent Perinatal

Transmission

Mother’s HBsAg Status:

Treatment Positive Negative Unknown
HBIGa Given within 12 hours None If positive, give within
of birth 7 days; if negative,
give none
AND
Hepatitis B vaccineb
Dose 1 Within 12 hours of birth Based on infant’s Within 12 hours of
weightc birth
Dose 2 At month 1–2 At month 1–2 At month 1–2
CHAPTER 21 / VIRAL HEPATITIS 349
Dose 3 At month 6 At month 6–18 At month 6
a
0.5 mL intramuscularly.
b
See Table
TABLE 21–2. 21–4 for appropriate
Interpretation hepatitis
of Viral B vaccine
Hepatitis dose.
Serology Panels
c
Full-term infants who are medically stable and weigh greater than or equal to 2000 grams born to
Hepatitis C
HBsAg-negative mothersLaboratory
should receive
Type Test the hepatitis
ResultB vaccine before Interpretation
hospital discharge. Preterm infants
of Panel
weighing
Lebih less than 2000
dariA 170juta orangIgM grams born to HBsAg-negative
terinfeksi dengan hepatitis mothers should
C diseluruh dunia receive the
dan lebih first dose of berada
hepatitisdi
Hepatitis
B vaccine 1 month after birthanti-HAV Negative
or at hospital discharge. Susceptible to dari 4 juta
infection
From Centers
negara DiseaseIgG
AmerikaforSerikat. anti-HAV
Control
Prevalensi and
lebih tinggi Negative
Prevention. A Comprehensive
pada Hispanic blacksImmunization Strategy to
(3.2%) dibandingkan Eliminate
non-hispanic
Transmission of Hepatitis B Virus
IgM anti-HAV Infection inPositive
the United States. Recommendations
Acutely infected of the Advisory
whites
Committee(1.5%) dan pria lebih
on Immunization mudah(ACIP)
Practices terinfeksi
Part 1:dibandingkan
Immunization wanita.
of Infants,Jalur utamaandtransmisi
Children, HCV
Adolescents.
IgG anti-HAV Positive
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm?s_cid=rr5416a1_e. Immune due to either natural infection
sebelumnya melalui16,
Accessed February transfuse
2006. darah namun saat ini risiko tersebut telah or HAV vaccine
turun dan saat ini karena
Hepatitis Ba HBsAg Negative Susceptible to infection
penggunaan alat kesehatan saat penggunaan obat
anti-HBc iv menjadi risiko terbesar transmisi HCV.
Negative
anti-HBs Negative
HBsAg Negative Immune due to natural infection
Patofisiologi anti-HBc Positive
Additionally, the durability (likelihood of developing
anti-HBs andPositive The subcutaneous dose of interferon alfa-2b (Intron A) in
sustaining HBeAg Terinfeksi melalui darah,
seroconversion) merupakan
is greater
HBsAg than virus
80% RNA
after untai
Negative tunggal
patients dariImmune
who keluarga
are dueFlaviviridae
HBsAg-positive
to hepatitis isdan genus
either 5 million units daily
B vaccination
treatment has been discontinued. anti-HBc
If interferon treatment Negative(better tolerated) or 10 million units three times weekly. The
Hepacivirus. Kerusakan pada hepar disebabkan karena peptide structural dan nonstructural
duration is extended to 12 to 24 weeks, HBsAg anti-HBs loss is observedPositive dose for HBsAg-negative patients is 5 to 6 million units three
menyebabkan replikasi virus
in about 10% of patients. HBsAg RNA terutama peptide PositiveNS5.
timesAntibodi melawan
weekly.Acutely HCV dose
infected
The approved (anti-HCV) dalam interferon alfa-2a
for pegylated
anti-HBc Positive
Pegylated interferon
darahismengindikasikan
interferon thatadanya is attached
IgM infeksitodengan
anti-HBc a poly-Positive (Pegasys)
HCV. Jika infeksi for chronic lama
berlangsung hepatitis
lebih Bdari
is 6180 mcg subcutaneously
bulan
ethylene glycol molecule that increases theanti-HBs half-life of the drug,Negativeonce weekly. Interferon doses may need to be adjusted in
dan replikasi virus terjadi ditandai dengan tingginya kadar HCV RNA maka orang tersebut menjadi
thus allowing once-weekly dosing versus thrice-weekly
HBsAg admin-Positive patients withChronically renal impairment.
infected
hepatitis
istration required for kronis dimanaformulation.
the unmodified sistem imun tidak
anti-HBc lagi mampu untuk
Pegylated Positive melawannya
Even though the begitu juga dengan
advantages limfosit T therapy include a
of interferon
IgM anti-HBc Negative
interferon is well tolerated and is superior
tidak efektif dalam melakukan in efficacy
anti-HBs to unmod-
eradikasi HCVyang finite duration of treatment,
kemudian menyebabkan kerusakan sel hepar secara
Negative
lack of resistance, and possible
26
ified interferon for the treatment of chronic HBsAghepatitis B. NegativeHBsAg loss or seroconversion
Four interpretations (development
possibleb of anti-HBs), there
bertahap.
Patients with chronic hepatitis B whoanti-HBcare HBeAg-negativePositive are several significant disadvantages. These include the need
may achieve undetectable HBV DNA levels anti-HBs and normalizeNegativefor subcutaneous injections, and more importantly, the pro-
ALT levels during treatment with any of the antiviral thera-Negativenounced adverse-effect
Hepatitis C anti-HCV Susceptible toprofile
infectionthat may require treatment dis-
pies; however, once treatment has ceased, anti-HCV
these endpointsPositive continuation.Acutely The mostor chronically
common infected
complaints include injection
c 27
Hepatitis D IgM anti-HDV
return to pretreatment values. Patients treated with unmod- Positive site reactions Acute
and HBV-HDV
flulike coinfection
symptoms of fevers, chills, joint pain, and
HDVAg Positive
ified interferon haveDiagnosa
an end-of-treatment response
hepatitis C ditandai
HBsAg dengan (defined
anti-HCV dalam muscle
asPositive aches.ditandai
serum, yaitu Systemic adverse
dengan adanyaeffects
HCVinclude
RNA anorexia, nausea,
undetectable HBV DNA and normal ALTHBeAg levels) ranging fromPositive diarrhea, fatigue, headache, insomnia, irritability, depression,
yang melakukan proses replikasi.
60% to 70%; however, the rate of anti-HBc sustaining virologicPositive alopecia, and dermatitis. Hematologic abnormalities are com-
response once therapyHepatitis E
has been IgM anti-HEV
discontinued is approximatelyNegativemon including Susceptible to infection
neutropenia, anemia, and thrombocytopenia,
20 IgG anti-HEV Negative
20%. Patients with HBeAg-negative chronic hepatitis B which require either a dose reduction or treatment discontinua-
IgM anti-HEV Positive
28 28,29 Acutely infected
should be treated with more than 12 months of therapy. tion. Uncommon side effects include cardiac arrhythmias, dia-
When the duration of interferon therapyIgG anti-HEV
is prolonged beyondPositive betes, thyroidImmune due to natural infection
disorders, amenorrhea, and vision disturbances.
12 months, undetectable HBV DNA may be sustained, as well
a
Centers for Disease Control and Prevention. Hepatology. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/
Bserology.htm. Accessed February 19, 2006.
as increasing the chance
b
(1) Mayofbelosing HBsAg.
recovering from acute HBV infection; (2) May be distantly Lamivudine
immune and test is not sensitive enough to detect
Factors associated
very with a higher
low level likelihood
of anti-HBs in serum; of(3) response to
May be susceptible Lamivudine
with a (Epivir-HBV)
false-positive is anbeoral
anti-HBc; (4) May syntheticlevel
undetectable cytosine nucleoside
of HBsAg present in the serum and the person is actually a carrier.
interferon therapycHepatitis
are baseline HBV DNA levels less than analogue having antiviral effects
D should be suspected in those who have HBsAg positivity. Hepatitis D may present as either coinfection where
against HIV and hepatitis
200 pg/mL and ALT bothconcentrations greaterappear
HDV and HBV serologies than simultaneously
5 times the whereasBforvirus. In patients
superinfection, HBV haswithbeenchronic hepatitis
present for B, lamivudine is
some time,
and later
upper limit of normal. 29 HDV develops.
effective in suppressing hepatitis B viral replication, normalizing
anti-HAV, hepatitis A antibody; anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; HBsAg,
hepatitis B surface antigen; anti-HCV, hepatitis C antibody; anti-HDV, hepatitis D antibody; anti-HEV, hepatitis E antibody;
HAV, hepatitis A virus; HBV, hepatitis B virus; HDV, hepatitis D virus; HDVAg, hepatitis D antigen; IgG, immunoglobulin
G; IgM, immunoglobulin M.
 of the disease. Liver damage and HCC are associated with high
levels
■
of hepatocyte apoptosis. Low levels of apoptosis are associ-
ated with viral persistence. Moreover, CD4 T-helper cells are
unlikely to mediate liver injury, but rather may promote an
cognized and many environment conducive for other immune responses damaging to
for infection is not the liver. Bystander killing may also play a role in hepatic damage.
apers for the screen- Although HCV infects less than 10% of hepatocytes, up to 20% of
ist.59,61 Screening is cells are activated for apoptosis.64
Penatalaksanaan hepatitis C
ction (Table 42–10). HCV poses a daunting challenge for immune control because of
Dari
its tabel
rapid viraldiketahui bahwa
diversification. HCVgenotip
genomicvirus hepatitis
mutations are C pada masing-masing
detect- bagian negara berbeda.
able within 1 year of infection. Resolved cases of HCV are defined
C Untuk bagian asiaresponse
tenggara vgenotip virus CD8
hepatitis C masuk dalam tipe 6.
by a vigorous T-cell with highly active and persistent

TABLE 42-11 Worldwide Hepatitis C Virus Genotype Distribution

e 1992 ■
Genotype
■
Region
1 Worldwide, especially United States, Northern Europe
liver disease 2 Worldwide, especially Northern Europe, Japan
xposure 3 India
4 Middle East, Africa
fection 5 South Africa
6 Hong Kong, Southeast Asia
From Hoofnagle.63

Rekomendasi terapi bagi pasien yang perlu pernah mendapatkan terapi hepatitis C dengan atau tanpa
sirosis menggunakan kombinasi ledipasvir 90mg/sofobusvir 400mg selama 12 minggu.
Rekomendasi lainnya, bagi pasien yang perlu mendapatkan interferon α (IFN), tanpa memperhatikan
■

status sirosis maka dibawah ini adalah pilihan terapi yang direkomendasikan yaitu sovobusvir 1x400mg
setiap hari, kemudian dikombinasi dengan ribavirin (RBV) dan peginterferon α-IFN (PEG-IFN) setiap
minggu selama 12 minggu.

Terapi yang tidak direkomendasikan bagi HCV yaitu penggunaan tunggal PEG-IFN, RBV atau bila
dikombinasi dengan simeprevir selama 24-48 minggu. Selain itu adalah penggunaan telaprevir atau
boceprevir

■
 ■

Sedangkan bagi pasien yang tidak bisa atau gagal dengan terapi PEG-IFN/RBV, maka pemberian
PEG-IFN dihentikkan dan RBV tetap di lanjutkan dengan dosis yang sama.
CHAPTER 21 / VIRAL HEPATITIS 349

TABLE 21–2. Interpretation of Viral Hepatitis Serology Panels

■

Type Laboratory Test Result Interpretation CHAPTER

of Panel 21 / VIRAL HEPATITIS 349
Hepatitis A IgM anti-HAV Negative Susceptible to infection
IgG anti-HAV Negative
TABLE
■
IgMof
21–2. Interpretation anti-HAV Positive Panels
Viral Hepatitis Serology Acutely infected
Monitoring yang perlu dilakukan pada penatalaksanaan HCV adalah
IgG anti-HAV Positive Immune due to either natural infection
Type Laboratory Test Result Interpretation of Panel
or HAV vaccine
Hepatitis
Hepatitis A
Ba IgM
HBsAganti-HAV Negative
Negative Susceptible
Susceptible to
to infection
infection
IgG anti-HAV
anti-HBc Negative
Negative
■ IgM anti-HAV
anti-HBs Positive
Negative Acutely infected
■ HBsAg
IgG anti-HAV Negative
Positive Immune due
Immune due to
to either
naturalnatural
infection
infection
anti-HBc Positive or HAV vaccine
anti-HBs Positive
Hepatitis
■
Ba HBsAg Negative Susceptible to infection
■ HBsAg
anti-HBc Negative
Negative Immune due to hepatitis B vaccination
anti-HBc
anti-HBs Negative
Negative
anti-HBs Positive
HBsAg Negative Immune due to natural infection
HBsAg
anti-HBc Positive
Positive Acutely infected
anti-HBc
anti-HBs Positive
Positive
IgM anti-HBc Positive
HBsAg Negative Immune due to hepatitis B vaccination
■
anti-HBs Negative
anti-HBc Negative
Hepatitis D
■
HBsAg
anti-HBs Positive
Positive Chronically infected
anti-HBc Positive
Ditandai dengan adanyaHBsAg
nilaianti-HBc
IgM
Positive
HBV untuk replikasi virus HDV. Pengukuran
Negative
Acutelykadar
infected
HDV RNA pada serum
anti-HBc Positive
anti-HBs Negative
melalui Polymerase ChainIgMReaction
anti-HBc (PCR). Adanya
PositiveIgM antibodies HDV Ag (IgManti-HD) menandakan
HBsAg
anti-HBs Negative
Negative Four interpretations possibleb
anti-HBc
penyakit sedang aktif danHBsAg Positive
IgG anti-HD menandakan
Positivejika infekti tidakChronically
dapat dihancurkan
infected secara spontan/
anti-HBs Negative
anti-HBc Positive
otomatis.
Hepatitis C anti-HCV
IgM anti-HBc Negative
Negative Susceptible to infection
anti-HBs
anti-HCV Negative
Positive Acutely or chronically infected
Hepatitis Dc HBsAg
IgM anti-HDV Negative
Positive Four
Acuteinterpretations possibleb
HBV-HDV coinfection
anti-HBc
HDVAg Positive
anti-HBs
HBsAg Negative
Positive
Hepatitis C HBeAg
anti-HCV Positive
Negative Susceptible to infection
anti-HBc Positive
anti-HCV Positive Acutely or chronically infected
Hepatitis E IgM anti-HEV Negative Susceptible to infection
Hepatitis Dc IgM anti-HDV Positive Acute HBV-HDV coinfection
IgG anti-HEV Negative
HDVAg Positive
Hepatitis E IgM anti-HEV
HBsAg Positive
Positive Acutely infected
HBeAg
IgG anti-HEV
Didasarkan pada adanya anti-HEV antibody. Positive Immune due to natural infection
anti-HBc Positive
a
Centers for Disease Control and Prevention. Hepatology. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/
Hepatitis E
Bserology.htm. IgM anti-HEV
Accessed February 19, 2006. Negative Susceptible to infection
b
(1) May be recovering fromIgG anti-HEV
acute HBV infection; (2)Negative
May be distantly immune and test is not sensitive enough to detect
very low level of anti-HBs in serum;
IgM (3) May be susceptible
anti-HEV Positivewith a false-positive anti-HBc;
Acutely (4) May be undetectable level
infected
of HBsAg present in the serum and the person is actually a carrier.
c IgG anti-HEV Positive Immune due
Hepatitis D should be suspected in those who have HBsAg positivity. Hepatitis D may present toas
natural
either infection
coinfection where
aboth HDV and HBV serologies appear simultaneously whereas for superinfection, HBV has been present for some time,
Centers for Disease Control and Prevention. Hepatology. Available at: http://www.cdc.gov/ncidod/diseases/hepatitis/b/
and later HDV develops.
Bserology.htm. Accessed February 19, 2006.
banti-HAV, hepatitis A antibody; anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; HBsAg,
(1) May be recovering from acute HBV infection; (2) May be distantly immune and test is not sensitive enough to detect
hepatitis B surface antigen; anti-HCV, hepatitis C antibody; anti-HDV, hepatitis D antibody; anti-HEV, hepatitis E antibody;
very low level of anti-HBs in serum; (3) May be susceptible with a false-positive anti-HBc; (4) May be undetectable level
HAV, hepatitis A virus; HBV, hepatitis B virus; HDV, hepatitis D virus; HDVAg, hepatitis D antigen; IgG, immunoglobulin
of HBsAg present in the serum and the person is actually a carrier.
cG; IgM, immunoglobulin M.
Hepatitis D should be suspected in those who have HBsAg positivity. Hepatitis D may present as either coinfection where
both HDV and HBV serologies appear simultaneously whereas for superinfection, HBV has been present for some time,
and later HDV develops.
anti-HAV, hepatitis A antibody; anti-HBc, hepatitis B core antibody; anti-HBs, hepatitis B surface antibody; HBsAg,
hepatitis B surface antigen; anti-HCV, hepatitis C antibody; anti-HDV, hepatitis D antibody; anti-HEV, hepatitis E antibody;
HAV, hepatitis A virus; HBV, hepatitis B virus; HDV, hepatitis D virus; HDVAg, hepatitis D antigen; IgG, immunoglobulin
G; IgM, immunoglobulin M.