Hepatitis

Ika Norcahyanti
Bagian Farmasi Klinik & Komunitas
Fakultas Farmasi UNEJ
Etiology…
Hepatitis B virus (HBV), is a double stranded DNA virus a
species of the genus Orthohepadnavirus, and a member of
the Hepadnaviridae family of viruses

Hepatitis C virus (HCV) is a small (55–65 nm in size), a single-

stranded RNA virus of the family Flaviviridae
Risk Factor - Hepatitis B…
 Persons born in regions of high or intermediate HBV
endemicity (HBsAg prevalence of  2%)
Africa (all countries)
North, Southeast, East Asia (all countries)
Australia and South Pacific (all countries except Australia and
New Zealand)
Middle East (all countries except Cyprus and Israel)
Eastern Europe (all countries except Hungary)
Western Europe (Malta, Spain, and indigenous populations of
Greenland)
North America (Alaskan natives and indigenous populations of
Northern Canada)
Risk Factor - Hepatitis B…
Mexico and Central America (Guatemala and Honduras)
South America (Ecuador, Guyana, Suriname, Venezuela, and
Amazonian areas)
Caribbean (Antigua-Barbuda, Dominica, Grenada, Haiti,
Jamaica, Saint Kitts and Nevis, Saint Lucia, and Turks and
Caicos Islands)
 U.S.-born persons not vaccinated as an infant whose parents
were born in regions with high HBV endemicity (8%)*
 Persons who have ever injected drugs*
 Men who have sex with men*
 Persons needing immunosuppressive therapy, including
chemotherapy, immunosuppression related to organ
transplantation, and immunosuppression for rheumatological
or gastroenterologic disorders.
Risk Factor - Hepatitis B…
 Individuals with elevated ALT or AST of unknown etiology*
 Donors of blood, plasma, organs, tissues, or semen
 Persons with end-stage renal disease, including predialysis,
hemodialysis, peritoneal dialysis, and home dialysis patients*
 All pregnant women
 Infants born to HBsAg-positive mothers*
 Persons with chronic liver disease, e.g., HCV*
 Persons with HIV*
 Household, needle-sharing, and sexual contacts of HBsAg-
positive persons*
 Persons who are not in a long-term, mutually monogamous
relationship (e.g., >1 sex partner during the previous 6
months)*
Risk Factor - Hepatitis B…
 Persons seeking evaluation or treatment for a sexually
transmitted disease*
 Health care and public safety workers at risk for occupational
exposure to blood or blood-contaminated body fluids*
 Residents and staff of facilities for developmentally disabled
persons*
 Travelers to countries with intermediate or high prevalence of
HBV infection*
 Persons who are the source of blood or body fluid exposures
that might require postexposure prophylaxis
 Inmates of correctional facilities*
Risk Factor - Hepatitis B…
 Unvaccinated persons with diabetes who are aged 19 through
59 years (discretion of clinician for unvaccinated adults with
diabetes who are aged 60 years)*
*Indicates those who should receive hepatitis B vaccine, if
seronegative.
Risk Factor - Hepatitis C…
 Current or former injection drug users
 Recipients of blood products (clotting factor concentrates
made before 1987, blood transfusions or solid organ
transplants before July 1992)
 Health care providers in contact with infected needles
 Chronic hemodialysis
 Individuals having multiple sexual partners
 HIV infection
 Perinatal transmission (< 5%)
 Unprofessional body piercing and tattooing
 Person born from 1945 through 1965
Clinical Presentation…
Symptoms
 Most patients infected with any type of viral
hepatitis have no symptoms
 Symptomatic patients may experience a flu-like
syndrome, fevers, fatigue/malaise, anorexia,
nausea, vomiting, diarrhea, dark urine, pale
appearing stools, pruritus, and abdominal pain
Clinical Presentation…
Signs
 Jaundice may be evident in the whites of the eyes
(scleral icterus) or skin
 An enlarged liver (hepatomegaly) and spleen
(splenomegaly) may be present
 Infulminant hepatitis with hepatic encephalopathy,
patients may have asterixis and coma
 In rare instances, extrahepatic symptoms may
develop arthritis, postcervical lymphadenopathy,
palmar erythema, cryoglobulinemia, and vasculitis
Diagnosis - Hepatitis B…
 Hepatitis B is diagnosed when HBsAg is detectable
in the serum,but HBsAg does not distinguish
between acute and chronic HBV
 The presence of IgM antibodies to HBcAg indicates
active infection
 IgG anti-HBc indicates either chronic infection or
possible immunity against HBV
Diagnosis - Hepatitis C…
 Hepatitis C is diagnosed by testing for anti-HCV in
the serum and confirmed by the presence of HCV
RNA

 HCV RNA levels quantify viral replication and are

used to determine if antiviral treatment for HCV is
effective. An HCV genotype should be obtained to
determine the likelihood of response to anti-HCV
therapy and the duration of treatment required
Prevention - Hepatitis B…
Hepatitis B Immune Globulin
 Hepatitis B immune globulin (HBIG) is a sterile solution
containing antibodies prepared from pooled human plasma
that has a high concentration of anti-HBs. A single dose of
HBIG 0.06 mL/kg is effective in providing passive
immunization in preventing CHB infections

 HBIG should only be administered intramuscularly

 The most common side effects of HBIG include erythema at

the injection site, headaches, myalgia, fatigue, urticaria,
nausea, and vomiting
Prevention - Hepatitis B…
Hepatitis B Vaccine
 Persons at high risk of acquiring the HBV should be
vaccinated with the hepatitis B vaccine at months 0, 1, and 6

 The hepatitis B vaccine dose depends on the person’s age

Prevention - Hepatitis C…
Currently,there are no vaccines available to prevent HCV, but
several are under development

Therefore, high-risk individuals should be tested for HCV

because most people are asymptomatic and unaware they are
infected
Prevention - Hepatitis C…
 Avoiding high-risk behaviors such as sharing needles among
IV drug users is the primary means of avoiding infection with
the HCV

 The risk of acquiring HCV through a blood transfusion

is 1 in 2 million since 1992, when widespread screening of
blood products and universal precautions took effect. It has
been estimated that more than 75% of individual infected
with the HCV were born during the baby boomer population;
therefore, the CDC now recommends that all people born
between 1945 and 1965 be tested at least once in their
lifetime for HCV
Treatment Goals…
 Prevent the spread of infection
 Prevent and treat symptoms
 Suppress viral replication
 Normalize hepatic aminotransferases
 Improve liver histology, and decrease morbidity and mortality by
preventing cirrhosis, HCC, and ESLD
 For hepatitis B, additional treatment goals include seroconversion or
loss of HBsAg, and seroconversion or loss of HBeAg.
 An additional goal for chronic hepatitis C is achieving undetectable
HCV RNA for at least 12 weeks after completing hepatitis C therapy,
known as achieving a sustained virologic response (SVR)
Treatment - Chronic Hepatitis B…
 The drug of choice for CHB depends on the patient’s
past medical history, ALT, HBV DNA level, HBeAg
status, severity of liver disease, and history of previous
HBV therapy

 The safety and efficacy profile of the medication and the

likelihood of developing drug resistance should also be
considered

 There are seven approved HBV agents: two

formulations of interferon alfa and five
nucleoside/nucleotide analogs
Treatment - Chronic Hepatitis C…
Treatment for chronic hepatitis C depends on the
patient’s past medical history, previous HCV
treatment history, severity of liver disease, and HCV
genotype
Treatment - Chronic Hepatitis C…
 Interferon/Pegylated Interferon and Ribavirin
 Direct-Acting Antiviral Agents—First Generation
 Direct-Acting Antiviral Agents—Second Generation
Outcome Evaluation - Hepatitis B…
 Obtain an ALT at baseline and then every 3 to 6 months
during hepatitis B treatment

 Monitor HBV DNA levels every 3 to 6 months to determine

treatment response

 Monitor HBeAg and anti-HBe every 6 months to determine

if seroconversion to anti-HBe occurred or HBeAg was lost in
HBeAg-positive CHB patients

 Monitor HBsAg every 6 to 12 months to determine if HBsAg

was lost or anti-HBs developed in CHB HBeAg-negative
patients with persistently undetectable serum HBV DNA
levels
Outcome Evaluation - Hepatitis B…
 Reevaluate at month 6 and either switch or add a more
potent hepatitis B antiviral agent to the current hepatitis B
regimen if the HBV DNA level has not decreased by 2 logs
after 6 months of therapy

 Continue treatment in CHB HBeAg-positive patients

until HBeAg seroconversion has been attained along with
undetectable HBV DNA levels. Once anti-HBe appears,
complete an additional 6 months of hepatitis B therapy

 Continue treatment in CHB HBeAg-negative patients until

HBsAg is lost

 Monitor closely for hepatitis flare and viral relapse when

discontinuing hepatitis B therapy
Outcome Evaluation - Hepatitis B…
 Obtain a CBC with differential every 4 weeks and
thyroidstimulating hormone (TSH) and fasting lipid panel
every 12 weeks when receiving pegylated interferon therapy
for hepatitis B

 Monitor serum creatinine for nephrotoxicity at baseline and

every 12 weeks for patients receiving tenofovir or adefovir

 Monitor creatine kinase at baseline and periodically (eg,

every 12 weeks) for patients taking telbivudine because
muscle weakness and myopathy have occurred
Outcome Evaluation - Hepatitis C…
 Sustained virologic response (SVR) is defined as having
an undetectable HCV RNA level at least 3 months
posttreatment; this is the ultimate goal of HCV therapy and
indicates a virological cure

 End of treatment response (ETR or EOT) is defined as having

undetectable HCV RNA levels at the end of treatment

 Biochemical response is defined as normalization of ALT;

monitor ALT levels every 4 weeks

 Histologic response is defined as improving inflammation

and fibrosis as documented by liver biopsy scores
Outcome Evaluation - Hepatitis C…
 Check the HCV RNA level per HCV guideline
recommendations to determine the effectiveness of the
HCV therapy and discontinue treatment if the HCV RNA
has not decreased or become undetectable at certain timepoints

 Monitor WBC, ANC, and platelets either weekly or biweekly

during the first month of therapy and monthly thereafter if
stable while on pegylated interferon

 Monitor hemoglobin levels weekly or biweekly during

the first month and monthly thereafter if stable while on
ribavirin

 Monitor for fatigue, shortness of breath, and chest pain and

dermatological complications while on ribavirin; if significant
complaints, discontinue treatment
Outcome Evaluation - Hepatitis C…
 Monitor TSH and fasting lipid panel every 12 weeks while
receiving pegylated interferon

 Monitor serum creatinine in patients receiving ribavirin

to detect renal insufficiency that may result in ribavirin
accumulation and toxicity (eg, hemolytic anemia)

 Conduct a thorough medication reconciliation of

prescription, over-the-counter, and dietary and herbal
supplements prior and during HCV therapy, especially if
prescribed a DAA

 Monitor total bilirubin concentrations every 2 to 4 weeks

while on simeprevir, and perhaps more often if the patient is
cirrhotic or has decompensated liver disease