TREATMENT OF VIRAL

HEPATITIS
PRESENTED BY;
DR.H.S.IMRAN-UL-HAQUE
ASST.PROF
DIMC
INTRODUCTION

• The most common types of viral hepatitis include hepatitis A (HAV), B

(HBV), C (HCV), D (HDV), and E (HEV).
• Acute hepatitis may be associated with all five types of hepatitis and
rarely exceeds 6 months in duration.
• Chronic hepatitis (disease lasting longer than 6 months) is usually
associated with hepatitis B, C, and D.
• Chronic viral hepatitis may lead to the development of cirrhosis and
may result in end-stage liver disease (ESLD) and hepatocellular
carcinoma (HCC).
• Complications of ESLD include ascites, edema, hepatic encephalopathy,
infections (eg, spontaneous bacterial peritonitis), hepatorenal syndrome,
and esophageal varices.
• Therefore, prevention and treatment of viral hepatitis may prevent ESLD
and HCC.
• Viral hepatitis may occur at any age and is one of the most common
causes of liver disease in the world.
• The true prevalence and incidence may be underreported because most
patients are asymptomatic.
Hepatitis-A
• Hepatitis A (HAV) HAV affects 1.4 million people yearly worldwide.
• The prevalence is highest in economically challenged and underdeveloped
countries.
• The numbers of acute HAV infections and hospitalizations have decreased
since the introduction of the HAV vaccine in 1995.
• HAV is primarily detected in contaminated feces and infects people via the
fecal–oral route.
• Outbreaks occur in areas of poor sanitation.
• There are no documented cases of chronic hepatitis A.
• Death from HAV is rare and mostly associated with fulminant hepatitis;
PATHOPHYSIOLOGY

• Hepatitis A is a non-enveloped single-stranded RNA virus

• The primary host for the HAV is humans, with hepatic cells as the
main site for viral replication.
• As part of the viral degradation process, the HAV is released into the
biliary system causing elevated HAV concentrations in the feces.
• Hepatitis A infections are usually self-limiting and do not lead to
chronic disease; rarely it may result in fulminant hepatitis.
General Approach

• Managing viral hepatitis involves both prevention and treatment.

• Prevention of hepatitis A and B (and indirectly for hepatitis D) can be
achieved with immune globulin (IG) or vaccines.
• Acute viral hepatitis is primarily managed with supportive care.
• Mild to moderate symptoms rarely require hospitalization, but
hospital admission is recommended in individuals experiencing
significant nausea, vomiting, diarrhea, and encephalopathy.
Hepatitis A Prevention

• Good personal hygiene and proper disposal of sanitary waste are

required to prevent HAV fecal–oral transmission.
• This includes frequent hand washing with soap and water after using
the bathroom and prior to eating meals.
• Individuals at risk of acquiring HAV should receive serum IG and/or
the hepatitis A vaccine.
▶ Immune Globulin
• IG is a solution containing antibodies from sterilized pooled human
plasma that provides passive immunization against HAV.
• IG is available as an IV (IGIV) or intramuscular (IGIM) formulation, but
only IGIM is used for prevention of HAV.
• IGIM does not provide lifelong immunity but is effective in providing
pre- and post-exposure prophylaxis against HAV.
• IGIM should be injected into a deltoid or gluteal muscle.
▶ Hepatitis A Vaccine
• Persons at risk of acquiring HAV should receive the hepatitis A vaccine
to provide pre- and postexposure prophylaxis.
• Two inactivated hepatitis A vaccines are available.
• The recommended regimen is to administer two injections 6 months
apart (at months 0 and 6).
Hepatitis B (HBV)

• It is a partially double-stranded DNA virus with a phospholipid layer

containing hepatitis B surface antigen (HBsAg) that surrounds the
nucleocapsid.
• Approximately 2 billion people worldwide have evidence of past or present
HBV infection, and more than 240 million people have chronic hepatitis B
(CHB).
• Globally, more than 680,000 deaths are associated with HBV annually.
• The primary modes of transmission of HBV are by blood and body fluids
through perinatal, sexual, or percutaneous exposure .
• Infants born to mothers who are infected with actively replicating HBV
have a 90% risk of becoming infected.
PREVENTION AND TREATMENT OF VIRAL
HEPATITIS
▶ Hepatitis B Immune Globulin (HBIG)
• HBIG is a sterile solution containing antibodies prepared from pooled
human plasma that has a high concentration of antiHBs.
• A single dose intramuscular of HBIG provides passive immunization
to prevent CHB infections.
▶ Hepatitis B Vaccine

• Two single-antigen hepatitis B vaccines are available.

• Persons at high risk of acquiring the HBV should be vaccinated at
months 0, 1, and 6.
• The hepatitis B vaccine is also indicated for post-exposure prophylaxis
to prevent CHB.
• Individuals exposed to HBV should receive the hepatitis B vaccine
with or without HBIG, preferably within 24 hours of exposure.
• Hepatitis B vaccine is not contraindicated during pregnancy and
should be safe to the fetus because it is an inactivated vaccine.
Chronic Hepatitis B Treatment
• The American Association for the Study of Liver Diseases (AASLD)
recommends treatment for CHB patients with persistently elevated
ALT (more than two times the upper limit of normal) or significant
histological disease and elevated HBV DNA levels greater than 20,000
IU/mL to delay progression to cirrhosis and prevent the development
of ESLD.
• Entecavir, tenofovir, and pegylated (peg) IFN-α2a are recommended
first-line therapies due to profound HBV DNA suppression.
• Adefovir, lamivudine, and telbivudine are not recommended due to
high rates of resistance.
• For all oral HBV agents, patients should be monitored for lactic
acidosis and severe hepatomegaly because some cases have been
fatal.
• Hepatic function tests should be monitored if treatment is to be
discontinued, because severe acute hepatitis exacerbations have
been reported.
• Dosage adjustments are required in patients with renal dysfunction
for all oral HBV regimens.
Interferons.
Mechanisms:
• IFN- is a cytokine.
• Acts through host cell surface receptors increasing the activity of Janus kinases
(JAKS).
• These enzymes phosphorylate signal transducers and activators of transcription
(STATS) to increase the formation of antiviral proteins.
• The selective antiviral action of IFN- is primarily due to activation of a host cell
ribonuclease that preferentially degrades viral mRNA.
• IFN- also promotes formation of natural killer cells that destroy infected liver
cells.
Pharmacokinetics
• There are several forms of IFN- with minor differences in amino acid
composition.
• Absorption from intramuscular or subcutaneous injection is slow.
• Elimination of IFN- is mainly via proteolytic hydrolysis in the kidney.
• Conventional forms of IFN- are usually administered daily or 3 times a
week.
• Pegylated forms of IFN- conjugated to polyethylene glycol can be
administered once a week.
Clinical Uses
• Interferon- is used in chronic HBV as an individual agent or in combination with
other drugs.
• When used in combinations with ribavirin, the progression of acute HCV infection
to chronic HCV is reduced.
• Pegylated IFN- together with ribavirin is superior to standard forms of IFN- in
chronic HCV.
Toxicity
• GI irritation.
• A flu-like syndrome.
• Neutropenia.
• Profound fatigue and myalgia.
• Alopecia.
• Reversible hearing loss.
• Thyroid dysfunction.
• Mental confusion, and severe depression.
Adefovir Dipivoxil
Mechanisms:
• Adefovir dipivoxil is the prodrug of adefovir.
• Its phosphorylation by cellular kinases, competitively inhibits HBV
DNA polymerase.
• Results in chain termination after incorporation into the viral DNA.
• HBV resistance to adefovir—though uncommon—has recently been
reported.
Pharmacokinetics and Clinical Use
• Adefovir has good oral bioavailability unaffected by foods.
• The drug is eliminated by the kidney, and dose reductions are
required in renal dysfunction.
• Adefovir has activity against lamivudine-resistant strains of HBV.
Entecavir
• Entecavir is a guanosine nucleoside that inhibits HBV DNA
polymerase.
• Effective orally.
• The drug has an intracellular half-life of more than 12 h.
• Renal elimination in part via active tubular secretion.
• Clinical efficacy is similar to that of lamivudine.
• There is cross-resistance between the 2 drugs.
• The drug causes headache, dizziness, fatigue, and nausea.
Lamivudine
• This nucleoside inhibitor of HIV reverse transcriptase.
• is active in chronic HBV infection.
• Has a longer intracellular half-life in HBV-infected cells than in HIV-infected cells.
• Thus can be used in lower doses for hepatitis than for HIV infection.
• Used as monotherapy, lamivudine rapidly suppresses HBV replication and is remarkably nontoxic.
• Coinfection with HIV may increase the risk of pancreatitis.
• Lamivudine–resistant HBV mutants emerge at a rate of about 20% per year if the drug is used
alone.
• On reappearance of detectable levels of HBV DNA, patients should be switched to IFN- or
adefovir.
 Tenofovir
• An antiretroviral drug.
• Also approved for chronic HBV infection.
• Active against lamivudine- and entacavir-resistant strains.
• Two types:1) Tenofovir alafenamide ( TAF)
2) Tenofovir disoproxil fumarate(TDF)
Nucleoside/Nucl Indication Dose ROA
eotide analog
Chronic hepatitis B 100 mg once daily Oral
Lamivudine

Adefovir Chronic hepatitis B 10 mg once daily Oral

Entecavir Chronic hepatitis B 0.5–1 mg once daily Oral

Tenofovir Chronic hepatitis B Oral

300 mg once daily

Telbivudine Chronic hepatitis B 600 mg once daily Oral

Interferons
Interferon alfa-2b Chronic hepatitis B 5 million units once daily Subcutaneous or
or 10 million units three intramuscular
times weekly
Pegylated interferon Chronic hepatitis B 180 mcg once weekly Subcutaneous
alfa-2a
THANK YOU