Hepatitis B & C

Presenter: Dr Moise Mathe

Department : Internal
Medicine/KIU

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Outline
1. General Information
2. Epidemiology
3. Etiology
4. Pathophysiology
5. Clinical features
6. Diagnostics
7. Management
8. Summary

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I. General Information
• Acute viral hepatitis is a common, worldwide disease that has
different causes; each type shares clinical, biochemical, and
morphologic features. The term acute viral hepatitis often refers to
infection of the liver by one of the hepatitis viruses. Other viruses
(eg, Epstein-Barr virus, yellow fever virus, cytomegalovirus) can also
cause acute viral hepatitis but less commonly.
• This presentation will only cover hepatitis B and C

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 I. Hepatitis B

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 I.1 Etiology

• Virus
Hepatitis B virus (HBV)
• Member of the Hepadnavirus family
• Circular, partially double-stranded DNA virus
• Transmission
• Frequency and patterns of transmission vary worldwide.
• Sexual: transmitted when bodily fluids come in contact with broken skin or mucous
membranes (mouth, genitals, or rectum)
• Parenteral
• Contaminated needles or instruments (body piercings, tattoos, and acupuncture)
• Blood transfusions or organ transplants
• Vertical transmission (mother-to-child transmission)
• Common associations
• Hepatitis C virus (HCV) and HIV-positive individuals
• Travelers to regions where HBV is endemic
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 I.2 Pathophysiology

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 I.2 Pathophysiology

Acute infection
• In acute infection, the cellular immune response causes damage to hepatocytes.
• Hepatitis B-infected hepatocytes express viral peptides on their surfaces → detection of the HBV-
derived peptides by lymphocytes and the subsequent activation of CD8+ T cells that attack the
infected hepatocytes → hepatic inflammation with destruction of hepatocytes
Chronic infection
• Caused by viral persistence due to failing immune clearance, which promotes:
• Persistent hepatic inflammation → necrosis, mitosis, and regeneration processes → cirrhosis and
cellular dysplasia → hepatocellular carcinoma (HCC)
• Integration of HBV DNA into the host genome → altered expression
of endogenous genes, chromosomal instability → HCC

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 I.3 Clinical Features
Acute hepatitis B virus infection

• Acute HBV infection is defined as infection acquired in the past 6 months.

• Incubation period: 1–6 months
• Clinical course: varies significantly
• Serum sickness-like syndrome can develop during the prodromal (preicteric) period 1–2
weeks after infection: rash, arthralgias, myalgias, fever
• Subclinical hepatitis (∼ 70% of cases)
• Symptomatic hepatitis (∼ 30% of cases; see also acute viral hepatitis)
• Fever, skin rash, arthralgias, myalgias, fatigue
• Nausea, anorexia
• Jaundice
• Right upper quadrant pain
• Symptoms usually resolve after a few weeks, but can last up to 6 months.
• May develop into fulminant hepatitis (∼ 0.5% of cases)

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 I.3 Clinical Features
Chronic hepatitis B virus infection

• Chronic HBV infection is defined as infection persisting for more than 6 months with
detection of HBsAg and, possibly, signs and symptoms of liver damage.
• Most patients are inactive, noncontagious carriers.
• Potential reactivation of chronic inactive hepatitis can manifest variably in the
following ways:
• Asymptomatic
• Unspecific symptoms
• Fatigue, malaise
• Nausea, poor appetite
• Unspecific abdominal pain
• Similar to acute hepatitis
• Hepatic failure
• The younger when infected, the more likely a patient develops chronic HBV
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 I.4 Diagnostics
Overview of HBV antigens and their corresponding antibodies
HBV antigen/DNA
Hepatitis B surface antigen (HBsAg)
Hepatitis B core antigen (HBcAg)
Hepatitis B e antigen (HBeAg)
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Description Corresponding antibodies
•Protein on the surface of HBV •Anti-HBs
•First evidence of infection • Indicates immunity to HBV due to
resolved infection or vaccination
•Presence for ≥ 6 months indicates a chronic • Usually appears within 3
infection. months of infection or vaccination
•Anti‑HBc
• Anti-HBc IgM: indicates recent
•Protein of the nucleocapsid infection with HBV (within ≤ 6
•Not routinely measured in clinical practice months)
• Anti-HBc IgG: indicates resolved or
chronic infection
•Protein secreted by
infected hepatocytes into the bloodstream
•Indicates active viral replication and •Anti‑HBe: indicates long-term clearance
thus high transmissibility and a poor of HBV and thus low transmissibility
prognosis
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 I.4 Diagnostics

HBV serology

• Initial tests ;
• HBsAg
• Anti-HBc
• Anti-HBs

• Further disease markers: indicated to assess disease activity if initial tests are positive
• HBeAg
• HBV DNA

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 I.4 Diagnostics
Interpretation of hepatitis B serology
HBsAg Anti-HBs Anti-HBc HBeAg Anti-HBe HBV DNA Transaminases

Undetectable
Acute infection ↑ Undetectable ↑ IgM ↑ Undetectable ↑ (ALT > AST)
or ↑

↑ IgM→ ↑ Ig Undetectable Undetectable

Window period Undetectable Undetectable Undetectable ↑ (ALT > AST)
G or ↑ or ↑

Active (high HBV DNA >

↑ Undetectable ↑ IgG ↑ Undetectable Normal or ↑
transmissibility) 2000 IU/mL
Chronic
infection
Inactive (low HBV DNA ≤
↑ Undetectable ↑ IgG Undetectable ↑ Normal
transmissibility) 2000 IU/mL

Resolved
↑ IgG ↑
infection
Immunity Undetectable ↑ Undetectable Undetectable Undetectable

HBV vaccination Undetectable Undetectable

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 I.4 Diagnostics

Additional laboratory studies

•Liver chemistries: elevated in acute infection, normal or elevated in chronic infection

• Mixed hyperbilirubinemia
• Ferritin
• ALP
• GGT
• ALT and AST
• AST:ALT ratio < 1 in acute infection
• AST:ALT ratio > 1 in chronic hepatitis may be a sign of cirrhosis.
•Laboratory diagnostics for cirrhosis
• ↓ Albumin, ↑ INR
• ↑ Bilirubin
• ↓ Platelets
•Evaluation of coinfection : Hep C, HIV

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 I.4 Treatment

Approach

•All patients
• Provide supportive care; as needed.
• Consider referral for liver transplantation in patients with:
• End-stage liver disease due to HBV
• Fulminant hepatic failure (emergency transplantation)
•Acute hepatitis B
• Antiviral therapy is generally not indicated.
•Chronic hepatitis B
• Assess the need for antiviral therapy

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 I.4 Treatment
Antiviral therapy for chronic hepatitis B
•Indications for antiviral therapy for HBV infection include:
• Cirrhosis or advanced fibrosis
• Acute liver failure
• Immunosuppression in HBV-positive patients
• Coinfection with HCV or HIV
• Family history of HCC
•Agents:
• Nucleotide reverse transcriptase inhibitors (NtRTIs), e.g., tenofovir disoproxil fumarate (TDF) or tenofovir
alafenamide (TAF)
• Nucleoside reverse transcriptase inhibitors (NRTIs), e.g., entecavir (ETV)
• Pegylated interferon alfa (PEG-IFN-α)
•Treatment regimens
• NtRTIs or NRTIs are usually the preferred option; treatment duration varies but can be indefinite.
• PEG-IFN

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Supportive care and patient education
•Avoid hepatotoxic medications.
•Advise alcohol cessation.
•Provide counseling on weight and diet changes to encourage weight loss as indicated.
•Educate patients on measures to prevent HBV transmission,

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 I.5 Complications
•Liver cirrhosis
•Hepatocellular carcinoma

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 I.5 Prevention
• Avoid exposure
• Vaccination
• Hepatitis B postexposure prophylaxis

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 I.5 Summary
• Hepatitis B is a viral infection caused by the hepatitis B virus (HBV). It occurs worldwide and is
transmitted sexually, parenterally, or vertically.
• After an incubation period of 1–6 months, most patients develop asymptomatic or mild inflammation of
the liver, which usually resolves spontaneously within a few weeks or months.
• However, 5% of adult patients and 90% of infants infected perinatally develop chronic hepatitis B (CHB).

• Individuals with CHB may be asymptomatic carriers or develop ongoing hepatic inflammation with an
increased risk of cirrhosis and hepatocellular carcinoma.

• Serologic testing initially includes measurement

of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs),
and hepatitis B core antibody (anti-HBc).
• CHB with persistent liver inflammation is characterized by detectable HBsAg and
elevated HBV DNA and ALT. Treatment of acute hepatitis B consists of supportive measures.
• For chronic active hepatitis B, nucleoside or nucleotide analogs (e.g., tenofovir) are the preferred agents
for reducing viral replication and infectivity.
• Prophylactic immunization with a recombinant vaccine is recommended for all age groups.

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 II. Hepatitis C

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 I.5 Definition
•Acute hepatitis C: HCV infection that develops during the first 6 months following the exposure
•Chronic hepatitis C: HCV infection that persists beyond 6 months following the exposure

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 II. 2 Etiology
Pathogen
• Hepacivirus C (Hepatitis C virus): RNA virus

Transmission
• Parenteral
• Needle sharing among individuals who use injection drugs
• Needlestick injury (e.g., health care workers)
• Blood transfusion
• Dialysis
• Organ transplantation
• Sexual: rare (in contrast to HBV and HIV)
• Perinatal (vertical)

Risk factors for HCV infection

• Injection drug use
• Hepatitis B virus or HIV positivity

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 II. 3 Clinical features
Incubation period
• 2 weeks to 6 months
Acute course
• Asymptomatic in 80% of cases
• Symptomatic
• Malaise, fever, myalgias, arthralgias
• RUQ pain, tender hepatomegaly
• Nausea, vomiting, diarrhea
• Jaundice, possibly pruritus

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 II. 3 Clinical features
Chronic course
• Seen especially in asymptomatic individuals (up to 85%), as the disease may go undiagnosed and
treatment may be delayed or never initiated (carrier state).
• Findings often mild, nonspecific (e.g., fatigue)
• Liver cirrhosis
• Extrahepatic features of HCV (common)
• Hematological
• B-cell non-Hodgkin lymphoma
• Autoimmune hemolytic anemia
• Purpura
• Renal
• glomerulonephritis
• Endocrine
• Diabetes mellitus
• Autoimmune thyroiditis

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 II. 4 Diagnostics
•Anti-HCV antibodies (EIA/ELISA immunoassay)
•HCV RNA (qualitative PCR):
• If anti-HCV antibody test is positive

Interpretation of hepatitis C tests

Anti-HCV antibodies
Negative Positive

•No infection •Resolved infection

Negative •Or false-
•Or within the window period positive antibody test

HCV RNA
•Active infection •Active infection (acute or
Positive • Within the window period chronic)
• Or patient is immunocompromised

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 II. 4 Diagnostics
Laboratory studies
•Routine studies
• Hepatocellular enzymes
• ↑ transaminases
• Cholestasis parameters
• ↑ GGT
• ↑ Alkaline phosphatase
• ↑ Bilirubin
• Liver synthetic function tests (alterations suggest cirrhosis)
• ↓ Albumin
• ↓ Total protein
• ↑ PT/INR

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 II. 5 Treatment
Antiviral therapy
HCV infection is always treated with a multidrug approach (no antivirals are approved as monotherapy).
• Direct-acting antivirals (DAAs)
• Antivirals target and inhibit HCV-encoded proteins that are essential for the HCV replication
cycle.
• Example regimens
• Sofosbuvir PLUS velpatasvir
• Ledipasvir PLUS sofosbuvir
• Interferon PLUS ribavirin

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 II. 5 Complications
•Liver cirrhosis
•Hepatocellular carcinoma
•Rarely fulminant hepatitis (liver failure)

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 II. 5 Prevention
•Primary prevention
• There is currently no effective preexposure or postexposure prophylaxis and
no vaccine against HCV infection.
• Use standard precautions for bloodborne pathogens in healthcare settings.
• Educate individuals with HCV infection about preventing transmission

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 II. 5 Summary
• Hepatitis C is an infection caused by the hepatitis C virus (HCV), which attacks liver cells and
causes liver inflammation. HCV is a bloodborne pathogen commonly transmitted through needlestick
injuries in health care settings, through shared drug-injection needles or transfusion.

• Screening plays a central role in detecting HCV infection because most infected individuals are
asymptomatic or mildly symptomatic.

• Approximately 85% of individuals with an acute infection that is not recognized and treated will
develop chronic hepatitis C, which is associated with cirrhosis, hepatocellular carcinoma, and increased
mortality.
• The presence of HCV antibodies and HCV RNA confirm the diagnosis.
• HCV infection can be safely and effectively treated with direct-acting antivirals (DAAs), which have cure
rates of over 95%.

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 Thank you

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 References
• Medscape
• Amboss

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