s B , C , a n d D

H e p ati ti
Gastroenterology 329

o ss, Se ung hwa n J , Jihwan H.

B
Contents
1. Hepatitis B, C, and D
a. Etiology
b. Pathophysiology
c. Transmission
d. Clinical manifestations
e. Diagnosis
f. Treatment
g. Complications
2. References
Hepatitis B
1. Etiology

HBV infection

Hepatitis B Virus (HBV)

Hepadnavirus family (DNA virus)
Enveloped, circular, icosahedral capsid

It is partially double stranded DNA virus

Hepatitis B
2. Pathogenesis

1.Endocytosis → Put into the nucleus →

Release partial double strand DNA →
100% double strand DNA → Use RNA
polymerase → Make viral mRNA →
Goes to ribosome → Make proteins
2. Double strand DNA → Pre-genomic
RNA → DNA → Double strand DNA →
Combine with proteins made by
ribosome
Make virus → Release from hepatocytes
→ Lysis to hepatocytes, MHC-1 with
viral proteins in outer parts of hepatocyte
→ TH1 cell comes to MHCI complex →
Perforin + Granzymes →Apoptosis to
hepatocytes
Hepatitis B
3. Transmission

1. Sexual contact
2. IV (Drug use, transfusion, needle
stick)
3. Maternal–fetal
Especially in 3rd trimester

Incubations period: 1 to 4 months

Hepatitis B
4. Clinical Manifestation
○ Fever
○ Malaise
○ Nausea, Vomiting
○ Anorexia
○ RUQ pain
○ Jaundice
○ Itching (Bile salts in skin)
○ Dark urine (Bilirubin)
○ Clay-colored stools (Lack of bilirubin
excretion)

Extrahepatic Manifestations
○ Polyarteritis nodosa
○ Glomerular disease
 Hepatitis B
5. Diagnosis
‣ Antigens
○ Hepatitis B surface antigen [HBsAg]
○ Hepatitis B e antigen [HBeAg]
‣ Antibodies
○ Anti-hepatitis B surface antigen [Anti-HBsAg]
○ Anti-hepatitis B e antigen [Anti-HBeAg]
○ Anti-hepatitis B core antigen [Anti-HBcAg]
‣ Antigens rise in acute disease, fall as infection resolves
‣ Antibodies rise as acute infection resolves
 Hepatitis B
5. Diagnosis(cont.)
‣ Acute
○ HBsAg (except window)
○ IgM Anti-HBc (even during window)
○ HBeAg (indicates infectivity)
○ HBV DNA
‣ Recovery after acute
○ Anti-HBs, Anti-HBe, Anti-HBc (IgG)
○ Undetectable HBsAg
○ Absence of HBV DNA
 Hepatitis B
5. Diagnosis(cont.)
‣ Prior vaccination
○ Anti-HbsAg only
○ Not anti-HBc or anti-HBe
‣ Chronic infection
○ HBsAg positive
○ If HbeAg positive = high infectivity
‣ If HBsAg is positive = patient is infected
‣ If HBsAg is negative = patient is NOT infected
 Hepatitis B
6. Treatment
‣ Acute
○ Usually treated with supportive care
○ Immunocompetent adults < 5% chance chronic disease
‣ Multiple treatments for chronic disease
○ Interferon
○ Entecavir, Tenofovir, Lamivudine (NRTI)
○ Other antiviral drugs
‣ Liver transplant
 Hepatitis B
7. Prevention
‣ Vaccination
○ Recipient: Newborns, Health care workers, HIV patients, etc.
‣ Precautions
○ Know the HBV status of any sexual partner
○ Avoid using any illegal drugs
○ Be cautious about body piercing and tattooing
○ Vaccinated before travel in advance
 Hepatitis B
8. Complications
‣ Cirrhosis
○ Lead to extensive liver scarring
‣ Hepatocellular carcinoma (HCC)
○ Chronic HBV will ↑ risk of HCC
‣ Acute liver failure
○ Results a liver transplant
‣ Reactivation of HBV
‣ Other diseases such as kidney disease or inflammation of blood
vessels
Hepatitis C
Etiology
The hepatitis C virus is a small,
enveloped, positive-sense single-
stranded RNA virus of the family
Flaviviridae. Hepatitis C is an
infection caused by the hepatitis C
virus (HCV) that attacks the liver and
leads to inflammation.
The World Health Organization
(WHO) estimates that about 71
million people globally have chronic
hepatitis C, with approximately
399,000 dying from this infection,
primarily due to cirrhosis and
hepatocellular carcinoma.
Hepatitis C
Transmission
- Transfusion of blood contaminated with hepatitis C virus (HCV) was once a leading
means of HCV transmission. Since 1992, however, the screening of donated blood for
HCV antibody sharply reduced the risk of transfusion-associated HCV infection.
- Persons who inject illicit drugs with nonsterile needles are at the highest risk for HCV
infection. In developed countries, most of the new HCV infections are reported in injection
drug users (IDUs). The most recent surveys of active IDUs in the United States indicate
that approximately one third of young (aged 18–30 years) IDUs are HCV-infected.
- Transmission of HCV to healthcare workers may occur via needle-stick injuries or other
occupational exposures. Needle-stick injuries in the healthcare setting result in a 3% risk
of HCV transmission. According to Rischitelli et al, however, the prevalence of HCV
infection among healthcare workers is similar to that of the general population.
- HCV may be transmitted via sexual transmission. However, studies of heterosexual
couples with discordant serostatus have shown that such transmission is extremely
inefficient
- HCV may also be transmitted via tattooing, sharing razors, and acupuncture
 Hepatitis C

Pathogenesis
HCV presumably binds to specific
receptor(s) and enters cells
through endocytosis, as do other
members of Flaviviridae. The viral
genome is translated into a
precursor polyprotein after
uncoating, and viral RNA is
synthesized by a virus-encoded
polymerase complex
 Hepatitis C
Clinical manifestation
Acute hepatitis C virus (HCV) infection becomes chronic in 70% of patients, which represents a high rate of
chronicity for a viral infection. Most patients with chronic hepatitis C are asymptomatic or may have
nonspecific symptoms such as fatigue or malaise in the absence of hepatic synthetic dysfunction. But in
presence of hepatic synthetic dysfunction following symptoms appear.
● mental status changes (hepatic encephalopathy),
● ankle edema
● abdominal distention (ascites), and
● hematemesis or melena (variceal bleeding).
Symptoms often first develop as clinical findings of extrahepatic manifestations of HCV and most commonly
involve
● Arthralgias (23%)
● Paresthesias (17%)
● Myalgias (15%)
● Pruritus (15%)
● Sicca syndrome (11%)
 Hepatitis C Other common extrahepatic manifestations
‣ Physical Examination include the following:

Signs in patients with decompensated liver disease ● Cryoglobulinemia

include the following: ● Membranoproliferative glomerulonephritis
● Idiopathic thrombocytopenic purpura
● Hand signs: Palmar erythema, Dupuytren
contracture, asterixis, leukonychia, clubbing
● Lichen planus
● Head signs: Icteric sclera, temporal muscle ● Keratoconjunctivitis sicca
wasting, enlarged parotid, cyanosis ● Raynaud syndrome
● Fetor hepaticus ● Sjögren syndrome
● Gynecomastia, small testes ● Porphyria cutanea tarda
● Abdominal signs: Paraumbilical hernia, ascites, ● Necrotizing cutaneous vasculitis
caput medusae, hepatosplenomegaly,
abdominal bruit
● Ankle edema
● Scant body hair
● Skin signs: Spider nevi, petechiae, excoriations
due to pruritus
 Hepatitis C
‣ Diagnosis
Because new HCV infections are usually asymptomatic, few
people are diagnosed when the infection is recent. In those
people who go on to develop chronic HCV infection, the
infection is often undiagnosed because it remains
asymptomatic until decades after infection when symptoms
develop secondary to serious liver damage.

HCV infection is diagnosed in 2 steps:

1. Testing for anti-HCV antibodies with a serological test
identifies people who have been infected with the virus.
2. If the test is positive for anti-HCV antibodies, a nucleic Differential Diagnoses:
acid test for HCV ribonucleic acid (RNA) is needed to
confirm chronic infection and the need for treatment. ● Autoimmune Hepatitis
● Cholangitis
● Viral Hepatitis
 Hepatitis C
Treatment
WHO recommends therapy with pan-genotypic direct-acting antivirals (DAAs) for all
adults, adolescents and children down to 3 years of age with chronic hepatitis C
infection. Treatment duration is short (usually 12 to 24 weeks), depending on the
absence or presence of cirrhosis

● Direct-Acting Antiviral Agents (DAAs)

● Interferons and Pegylated Interferons

● Interferons and Ribavirin

 Hepatitis C
Prevention
There is no effective vaccine against hepatitis C so prevention depends on reducing the risk of
exposure to the virus in health care settings and in higher risk populations. This includes people
who inject drugs and men who have sex with men, particularly those infected with HIV or those who
are taking pre-exposure prophylaxis against HIV.

Primary prevention interventions recommended by WHO include:

● safe and appropriate use of health care injections;

● safe handling and disposal of sharps and waste;
● provision of comprehensive harm-reduction services to people who inject drugs;
● testing of donated blood for HBV and HCV (as well as HIV and syphilis);
● training of health personnel; and
● prevention of exposure to blood during sex.
 Hepatitis D
1. Etiology
‣ IVDU
‣ HBV-DNA measured below 2000 IU/mL
‣ Alanine aminotransferase (ALT) level above 40 U/L
‣ HDV endemicity at the country of origin

‣ Sexual transmission is less efficient than with HBV

‣ Perinatal transmission is rare
 Hepatitis D
2. Pathophysiology
‣ ‘Defective virus’
‣ Lacks genes for envelope proteins
‣ Uses HbsAg for envelope protein

‣ Invades hepatocytes → Travels to nucleus to replicate → Uses HBV to

provide envelope → Virus particle coated with HBsAg → Uses host cell
RNA polymerase to replicate genome
 Hepatitis D
3. Transmission
‣ Co-infected with HBV
‣ HDV infections in setting of chronic HBV carrier state
‣ Superinfection often leads to flare of hepatitis

4. Clinical manifestations
‣ 90% of patients are asymptomatic
‣ Incubation period is 21-45 days but may shorter in cases of superinfection
‣ Jaundice, dark urine, abdominal pain(RUQ), nausea with vomiting,
confusion, bruising, and bleeding (rare), pruritus, scleral icterus
‣ Rare: Encephalopathy, petechiae with bruising
Hepatitis D
5. Diagnosis

○ Serology Test
Need HBV (+)

Acute: HDV RNA (+), HDV Ag (+), Anti- HDV

(IgM, +)

Chronic: HDV RNA (+), HDV Ag (-),

Anti -HDV (IgG, +)
Hepatitis D
Co- infection: Both HDV and HBV are contracted
simultaneously

-> Depending on the relative amounts to of HBV

and HDV, one or two episodes of hepatitis occurs

Superinfection: Occurs when chronic HBV

carriers are infected with HDV

-> Severe acute hepatitis and chronic Hepatitis D

infection (80%)
Hepatitis D
6. Treatment
Treatment for chronic HBV infection can
also benefit people with HDV infection.

Interferon alpha and pegylated interferon

alpha have been shown to be effective in
reducing HDV RNA levels.

7. Prevention
○HBV vaccination help prevent HDV
infection.
○Passive prophylaxis with HB
immunoglobulin
Hepatitis D

1. Cirrhosis
2. Increased risk of liver
cancer
3. Fulminant hepatitis
4. Increased risk of liver
transplant failure
5. Ascites
6. Hepatic encephalopathy
7. Gastrointestinal bleeding
Thank You For Your Attention
 References
emedicine.medscape.com. (n.d.). Hepatitis D Clinical Presentation: History and Physical Examination. [online] Available
at: https://emedicine.medscape.com/article/178038-clinical [Accessed 14 May 2023].

Mayo Clinic (2017). Hepatitis B - Diagnosis and treatment - Mayo Clinic. [online] Mayoclinic.org. Available at:
https://www.mayoclinic.org/diseases-conditions/hepatitis-b/diagnosis-treatment/drc-20366821.

https://www.who.int/news-room/fact-sheets/detail/hepatitis-c#:~:text=HCV%20infection%20is%20diagnosed%20in,and
%20the%20need%20for%20treatment.