Hepatitis

Irma Abashidze
Hepatitis A
Etiology
•Pathogen: hepatitis A virus
• Belongs to the family of Picornaviridae and the genus Hepatovirus
• Small (27 nm in diameter), non-enveloped virus with single-stranded, positive-sense RNA
• Resistant to denaturation by gastric acid, heat, and chemicals, and can remain viable for months in fresh and saltwater
• Humans are the only reservoir for the hepatitis A virus.
•Route of transmission: fecal-oral
• Contaminated water and food (e.g., raw shellfish)
• Risk groups: international travelers, nursing home residents, prison inmates, men who have sex with men, IV drug users.
•Infectious period: 2 weeks before to 1 week after the onset of the illness
Clinical features
HAV infection in children is typically asymptomatic. The risk of symptomatic disease increases with age
and coinfection (e.g., with hepatitis B).
•Incubation period: 2–6 weeks
•Phases of acute viral hepatitisProdromal phase: 1–2 weeks
• Right upper quadrant pain, tender hepatomegaly
• Fever, malaise
• Anorexia, nausea, vomiting
• Icteric phase: ∼ 2 weeks
• Jaundice
• Dark urine and pale stools
• Pruritus
• Resolution of symptoms
Diagnostics
Laboratory testing
•Routine studies
• ↑ Serum transaminase levels (AST, ALT)
• AST/ALT ratio is usually < 1
• ↑ Total bilirubin and urine bilirubin
• ↑ ALP, ↑ GGT
•Confirmatory testing
• ↑ Anti-HAV IgM antibodies: present in patients with active infection
• Usually detectable 5–10 days after exposure and 5–10 days before clinical symptoms develop
• Levels peak commonly ∼ 1 month after infection.
• May persist for up to 6 months after infection
• ↑ Anti-HAV IgG antibodies
• Develop during active infection and persist indefinitely after infection or vaccination
• Production begins within 2–3 weeks of infection.
• HAV RNA can be detected in stool and serum samples using PCR.
Treatment
•Hepatitis A is generally self-limited.
•Offer supportive care.
• Recommend rest as needed.
• Consider symptomatic treatment, e.g., antiemetics.
• Inability to maintain hydration with oral fluids can be an indication for parenteral fluid therapy and hospitalization.
•Recommend alcohol avoidance.
•Use medications that are metabolized by the liver with caution (e.g., acetaminophen).
•More intensive treatment may be required in rare cases in which hepatitis A leads to acute liver failure
Prevention
Hepatitis A preexposure prophylaxis
•Advise all travelers to follow primary preventive measures such as food and water safety.
Hepatitis A vaccine
See “ACIP immunization schedule” for scheduling details.
•Recommend routine active immunization for:
• All children > 12 months of age
• Individuals at increased risk of HAV infection, including those who:
• Are traveling to a country in which HAV is endemic
• Expect to be in close contact with an adoptee from a country in which HAV is endemic
• Have a potential occupational exposure to HAV
• Are men who have sex with men
• Use injection or noninjection drugs
• Have unstable housing
• Individuals at increased risk of severe disease
• Individuals with chronic liver disease
• Adults and children > 12 months of age with HIV
• Any individual requesting to be vaccinated
•Consider active immunization for:
• Individuals in settings with people at increased risk of infection (e.g., homeless shelters, needle exchange programs, group homes)
• Individuals at increased risk of HAV infection, including currently or recently incarcerated individuals, during outbreaks
•Two single-antigen inactivated hepatitis A vaccines and one combination hepatitis A and hepatitis B inactivated vaccine are available in the US.
Hepatitis B
Etiology
Virus
•Hepatitis B virus (HBV)
• Member of the Hepadnavirus family
• Circular, partially double-stranded DNA virus
•See “General virology” for more information on viral structure.
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 (including those for procedures like body piercings, tattoos, and acupuncture) that come into contact
with the patient's blood
• 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
Risk factors for HBV infection and groups at risk
•Vertical transmission
• Individuals born in countries with medium-to-high HBV prevalence (≥ 2%)
• Unvaccinated children born to parents from countries with high HBV prevalence (≥ 8%)
• Infants born to HBsAg-positive individuals
•Parenteral or sexual transmission
• Injection drug use (current or previous)
• History of sexually transmitted infections or multiple sexual partners
• Sex workers
• Men who have sex with men
• Household, sexual, or needle-sharing contacts of individuals with HBV
• Current or previously incarcerated individuals
• Health care personnel (e.g., needlestick injury)
• HIV infection
• HCV infection (current or past)
• Chronic liver disease
• End-stage renal disease
• Dialysis
Pathophysiology
Replication cycle of HBV
HBV carries a DNA polymerase with both DNA and RNA-dependent functions, also known as reverse transcriptase (RT).
1.After entering the host cell's nucleus, reverse transcriptase completes the positive strand of the virus's partially double-stranded relaxed circular
DNA (rcDNA).
2.The rcDNA is converted to covalently closed circular DNA (cccDNA) primarily by host enzymes in a process that is not entirely understood.
3.The cccDNA is then transcribed into viral mRNA by host RNA polymerase.
4.The viral mRNA leaves the nucleus and is translated into HBV core proteins and new reverse transcriptase in the cytoplasm.
5.Viral mRNA and reverse transcriptase are packaged into a capsid, where viral mRNA is then reverse-transcribed into viral rcDNA.
6.New viral DNA genomes are enveloped and leave the cell as progeny virions.
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
•HBV proteins fulfill numerous immune-modulating functions that allow them to elude detection by the immune system and avoid clearance
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)
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
Indications for HBV screening Obtain initial HBV serology for the following individuals

• All individuals aged ≥ 18 years: at least once per lifetime

•Pregnant individuals: once per pregnancy, preferably in the first trimester (see “Perinatal hepatitis B”) Individuals with
risk factors for HBV infection
•Patients with elevated transaminases of unknown etiology
•Blood and tissue donors
•Individuals who require immunosuppression
•Any individual who requests screening
Hepatitis C
Etiology
Pathogen
•Hepacivirus C (Hepatitis C virus): RNA virus of the Hepacivirus genus and Flaviviridae family
•The risk of chronic infection is multifactorial and depends on the host's ability to clear the pathogen through activation
of multiple innate immunity pathways against the viral envelope.
• Flawed proofreading capability of RNA-dependent RNA polymerase (no 3′– 5′ exonuclease activity) introduces
mutations into genes encoding viral glycoprotein. envelope and enabling novel antigen production.
• Rapid replication rate produces many antigenically unique viral envelopes.
• Infection persists because the production rate of new mutant virions exceeds the production rate of host
antibodies.
•There are six genotypes: In the US, the main ones are genotype 1 (65–80%) and genotype 2 (10–15%).
•Reinfection with another HCV genotype is possible.
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)
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
•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). •Renal
• Findings often mild, nonspecific (e.g., fatigue) •Membranoproliferative glomerulonephritis (more
• Liver cirrhosis (up to 25% of cases) within 20 years of infection common)
• Extrahepatic features of HCV (common) •Membranous glomerulonephritis
• Hematological •Rheumatological
• Mixed cryoglobulinemia •Polyarteritis nodosa
• Lymphoma (especially B-cell non-Hodgkin lymphoma) •Sjogren syndrome
• ITP •Dermatological
• Autoimmune hemolytic anemia •Porphyria cutanea tarda
• Monoclonal gammopathies •Lichen planus
•Endocrine
•Diabetes mellitus
•Autoimmune thyroiditis (may lead to hypothyroidism)
•Vascular: leukocytoclastic vasculitis
•Others: sialadenitis
Individuals without risk factors for HCV infection
•All individuals aged ≥ 18 years: at least once per lifetime
•Pregnant individuals: once per pregnancy
The CDC recommends against universal screening in settings where HCV disease prevalence is < 0.1%.
Individuals with risk factors for HCV infection
•One-time screening
• Upon diagnosis with HIV
• Individuals < 18 years of age with risk factors for HCV infection
• Infants born to HCV-positive mothers
•Repeat screening
• Screening after recent exposure to HCV (e.g., health care personnel exposure)
• Initial screening: ideally within 48 hours of exposure
• Repeat testing: ≥ 6 months after exposure (if the initial test is negative)
• Annual screening
• People who recreationally inject drugs
• Men with HIV infection who have unprotected sex with men
• Men who have sex with men taking HIV preexposure prophylaxis
•Other indications
• Periodically based on individual risk factors for HCV infection
• On patient request