Viral Hepatitis

VIRAL HEPATITIS

Definition of Viral Hepatitis

  • General Term: Refers to liver infections caused by distinct types of hepatitis viruses.

  • Differentiation: Each hepatitis virus is etiologically and epidemiologically different.

Sign of Viral Hepatitis

  • Jaundice: The most notable sign of general hepatitis.

    • Description: Yellow discoloration of the skin and conjunctiva of the eyes.

    • Cause: Caused by accumulation of bile pigments in the blood due to liver damage, which hampers the liver’s ability to filter these pigments.

Historical Perspective

  • Early Civilizations:

    • Ancient Mesopotamia regarded the liver as the seat of life or soul.

    • Mesopotamian doctors performed examinations of liver from animals to forecast illnesses.

    • Liver disease and jaundice were known to Babylonian and ancient societies.

    • Scattered outbreaks of jaundice recorded from the 17th to 19th centuries.

Campaign Jaundice

  • Military Context: Term referring to hepatitis's prevalence among soldiers.

    • Symptoms included dark urine, transient fever, nausea, and anorexia preceding jaundice.

  • Blood-Transmitted Hepatitis: Documented first in 1885 after an outbreak among shipyard workers post-smallpox vaccination.

    • Identified improperly sterilized syringes as a cause.

    • Links established between hepatitis and tattoos.

Establishment of Blood Serum Transmission

  • In the late 1930s, transmission via blood was established.

    • Example: In 1937, ~40% of recipients from a single batch of human measles convalescent serum developed jaundice after an incubation period of up to 114 days.

Distinction of Hepatitis Types

  • In 1947, infectious epidemic hepatitis was differentiated from serum hepatitis.

Hepatitis Viruses

  • Acute Self-Limited Hepatitis:

    • Hepatitis A virus

    • Hepatitis E virus

  • Persistent Chronic Hepatitis:

    • Hepatitis B virus

    • Hepatitis C virus

    • Hepatitis D virus

    • Hepatitis F virus

    • Hepatitis G virus

Unknown Infections

  • Approximately 15% to 17% of hepatitis infections remain unexplained.

Hepatitis B Virus

  • Discovery: In 1963, research led by Dr. Blumberg discovered the Australian antigen from blood samples, linking it to serum hepatitis.

  • Dane Particle: Identification of the complete hepatitis B virion in 1970 named after the researcher who discovered it.

  • Classification: Hepatitis B virus (HBV) is categorized as a Hepadnavirus.

Characteristics of Hepadnavirus

  • Contains an unusual partly double-stranded and partly single-stranded circular DNA genome.

  • Reverse transcriptase generates genome DNA from a pre-genome RNA during virus assembly.

  • Produces large amounts of non-infectious spherical and filamentous particles.

HBV Composition

  • Main Components:

    • HBsAg: Surface antigen (Australian antigen)

    • HBcAg: Core antigen

    • HBeAg: Endogenous DNA polymerase associated with virus replication.

Table 1: Hepadnaviridae Family Characteristics
Current Statistics: Worldwide
Current Statistics: United States

  • Approximately 1 in 50 Americans (~6.6 million) have been infected.

  • Acute hepatitis B infection rates rose by 50% to 450% in states affected by the opioid crisis.

  • Estimated 2.4 million are chronically infected, predominantly adult males aged 25-44.

  • Approximately 23% of cases are transmitted sexually.

Transmission Methods of HBV

  • Blood Route: Transfusion, needle sharing (illicit drug use), tattooing, ear piercing, human bites.

  • Sexual Activities: Anal sex, vaginal intercourse and (potentially) oral sex.

    • High levels of HBV present in saliva, semen, and cervical secretions.

  • Mother to Newborn: At birth, potential transplacental transmission, breast milk (uncertain).

  • Casual Contact: Unlike HIV, can transmit through shared items (eating utensils, drinking glasses).

Clinical Disease of Hepatitis B Virus

  • Disease course varies widely.

    • Types of Hepatitis:

    • Inapparent Subclinical

    • Anicteric Hepatitis: Symptoms without jaundice.

    • Icteric Hepatitis: Symptoms with jaundice.

    • Chronic Hepatitis: Carrier state.

    • Fulminant Hepatitis: Can lead to death.

  • Incubation Period: Ranges from 45 - 120 days.

Predicted Outcomes in Adults

  • Subclinical or Anicteric Hepatitis: 65 - 80%.

  • Icteric Hepatitis: 20 - 35%.

  • Full Recovery: 90 - 98%.

  • Chronic Disease: 2 - 10%.

  • Mortality: 0.2 - 0.5% overall; 0.5 - 1.5% for icteric disease only.

Chronic Infection

  • 2 - 10% of adult patients may become lifelong carriers, mostly asymptomatic but can show liver abnormalities.

  • Fatigue, loss of appetite, and malaise can occur; jaundice is uncommon.

Carrier State by Age

Age Group

Carrier Likelihood

Adults

2-10%

Children < 5

25-50%

Newborns

~90%

HBV Antigens

  • HBsAg: Surface antigen, indicates past infection, induces protective antibodies.

  • HBcAg: Core antigen, indicates past infection.

  • HBeAg: Correlates with active replication.

Antibody Profiles: Diagnostic Value

Antibody

Indication

IgM Anti-HBc

Most sensitive for acute infection.

IgG Anti-HBs

Past infection, neutralizing antibody, immune protection.

IgG Anti-HBc

Past infection.

IgG Anti-HBe

Active infection, correlates with chronic state.

Incidence & Risk of Infection Comparison: HBV vs. HIV-1

  • Hepatitis B is 50 - 100 times more infectious than HIV-1.

    • HBV Concentrations: $10^8 - 10^{10}$ particles/ml.

    • HIV Concentrations: $10^{6} - 10^{8}$ particles/ml.

    • Needle-stick Risk: HBV ~18%; HIV <0.5% with known status.

  • Survival in Clinical Specimens: HBV survives up to 7 days; HIV reduces viability within hours.

Treatment & Control of Hepatitis B

  • Prophylaxis: Hepatitis B Immune Globulin (HBIG).

  • Acute Infection: No antiviral treatment available.

  • Chronic Infection: Interferon-alpha shows effectiveness in 25-40% cases; several reverse transcriptase inhibitors reduce HBeAg levels significantly.

Hepatitis B Virus and Liver Cancer

  • Chronic carriers have 270X greater likelihood of developing liver cancer.

  • Liver cancer is the leading cause of cancer deaths in Asia and affects a significant portion of cancer patients in Africa.

Vaccine Development History

  • 1970s: Hepatitis B Virus issues among homosexual men; higher infection rates than the general population.

  • Vaccine Development:

    • Manufactured from Dane particles derived from human carriers.

    • Process: Blood collection via plasmaphoresis, purification, and inactivation for safety.

Clinical Trials for Hepatitis B Vaccine

  • Phase I Trials: 1,083 volunteers; seroconversion rates after vaccination (81% after 1 injection, 96% after 3 injections) demonstrated vaccine efficacy.

Types of Vaccines

  • Plasma-derived Vaccine: Extracted from human carriers but halted due to HIV fears (unfounded).

  • Recombinant Vaccine: Produced using yeast to express HBsAg, providing >90% immunity in healthy adults.

Vaccination Recommendations

  • Recommended for high-risk groups including healthcare workers, morticians, hemodialysis patients, certain drug users, and sexual partners of carriers.

Hepatitis C Virus

  • Discovery Timeline: Non-A, non-B hepatitis identified in the mid-1970s; hepatitis C virus discovered via molecular techniques in 1987, published in 1989.

  • Classification: Belongs to the family Flaviviridae.

Current Statistics: Worldwide and U.S.

  • Approximately 150-200 million individuals worldwide are infected, with roughly 58 million having chronic infections.

  • New infections rose significantly post-opioid crisis; 400,000 deaths annually from hepatitis C.

Transmission of Hepatitis C

  • Primary Route: Blood transfusion, needle sharing, tattooing.

  • Sexual Transmission: Unclear linkage; high-risk sexual activities can increase risk but not conclusively shown.

  • Mother-to-Child Transmission: Less than 10% chance; no evidence for breastfeeding-related transmission.

Clinical Disease of Hepatitis C

  • Acute Infection: Mild vague symptoms; spontaneous resolution in many cases.

  • Chronic Infection: Develops in ~80%; can lead to significant liver issues over time, including cirrhosis or liver cancer.

Treatment of Hepatitis C

  • Acute: Often untreated due to a lack of awareness; previously, combination therapies utilized.

  • Chronic: Various antiviral combinations yielding high clearance rates in treated individuals.

No Available Vaccine for Hepatitis C

  • Challenges: Genetic diversity of the virus and ethical limitations on traditional research methods like using chimpanzees.

Hepatitis A Virus

  • Family: Part of the picornavirus family.

  • Current Statistics: ~4,000 new U.S. cases in 2016; rarely fatal and no chronic infections reported.

Transmission of Hepatitis A

  • Associated with poor sanitation, contaminated water/milk/oysters, but not associated with sharing household items or sexual activities.

Clinical Disease of Hepatitis A

  • Incubation: 12 - 50 days; asymptomatic yet infectious during replication in the gut.

  • Icteric Phase begins following the initial symptoms, leading to symptoms of jaundice and liver enlargement.

Predicted Outcomes and Diagnosis

  • High likelihood of asymptomatic cases, especially in children.

  • Complete recovery is common; no chronic disease observed.

Diagnostic Approaches and Treatment

  • No antiviral drugs available; prevention through vaccination is crucial, with killed vaccines providing effective immune responses after administration within an appropriate timeframe.