Hepatitis A: Causes and Transmission

Hepatitis

• Inflammation or injury to the liver is marked by inflammatory cells in liver tissue.
• Causes include toxins, drugs, alcohol abuse, and bacterial/viral infections.

Hepatitis Viruses

• Viral hepatitis is a systemic condition primarily affecting the liver.
• Most acute cases in children/adults are caused by hepatitis viruses A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV).
• These hepatitis viruses cause acute liver inflammation and can cause clinical illnesses with fever, gastrointestinal distress (nausea/vomiting), and jaundice.

Hepatitis A

• HAV is a member of the picornavirus family, and its particle size is 27-32 nm.
• It has a linear, single-stranded RNA genome.
• HAV has only one known serotype.
• Transmitted via the fecal-oral route, HAV appears in feces.
• HAV is inactivated by heating food above 85°C for 1 minute or disinfecting surfaces with a 1:100 dilution of chlorine bleach.
• Extra precautions are necessary for hepatitis patients and their products given HAV's resistance to disinfection.
• HAV is widespread globally and outbreaks of Type A hepatitis are common in families, institutions, summer camps, day care centers, neonatal intensive care units, and military troops.
• Viral replication primarily happens in hepatocytes and results in severe cytopathology and impaired liver function.
• Persistent infection and chronic hepatitis is uncommon.
• Hepatitis A infection is most common in developing countries, often due to poor sanitation.
• HAV is transmitted by contaminated needles/syringes or through blood administration, but this is rare.

Hepatitis A Diagnosis

• Diagnosis involves marked elevation of liver transaminases and bilirubin.
• Detection of anti-HAV IgM indicates recent infection with positive findings for 4-6 months as immunoglobulin M (IgM) peaks about 2 weeks after elevation of liver enzymes, and declines to undetectable levels within 3–6 months.
• Detection of anti-HAV IgG indicates past infection, its detection in an acutely infected patient confirms the diagnosis. Anti-HAV IgG appears after disease onset and persists for decades.
• HAV can be detected in the liver, stool, bile, and blood using RIA, PCR, or immune electron microscopy. The virus appears early in the disease and disappears within 2 weeks after jaundice onset.

Hepatitis A Prevention and Treatment

• Prevention involves good hand hygiene, water chlorination, or boiling.
• Fecal contamination of food and water should be avoided.
• The inactivated Havrix vaccine is recommended IM for children > 1 year living in endemic countries, with 2 doses given 6 months apart the vaccine gives better than 95% protection for decades.
• Groups at increased risk of acquiring hepatitis A (injection/non-injection drug users, clotting factor disorders, people working with nonhuman primates and people with chronic liver disease) should be vaccinated.
• Immune globulin (IG) from normal adult plasma gives passive protection to 90% of those exposed within 1–2 weeks this is not effective after this time.
• Generally prescribed doses of IG do not prevent infection, but rather makes it mild and allows for active immunity.
• There is no specific antiviral treatment, but supportive care is recommended with sufferers are advised to rest, avoid fatty foods, eat a well-balanced diet, and stay hydrated.

Hepatitis B

• HBV is the only human hepatitis virus with a DNA genome.
• It is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

Hepatitis B Epidemiology

• HBV is distributed worldwide.
• It is found in blood, semen, saliva, and breast milk, which serve as sources of infection.
• Viral load can reach 10¹⁰ virus particles per ml.
• Mainly affects infants in developing nations.
• There are more than 350 million HBV carriers.
• HBV-related liver disease and hepatocellular carcinoma account for 600,000 deaths a year worldwide.
• Egypt has an HBV prevalence of 1.4% among adults aged 15-59.
• Transmission during infancy: infected mothers to newborns during delivery, or infected household contacts.
• No seasonal trend or specific age, but high-risk groups include parenteral drug abusers, healthcare workers, multiply transfused/organ transplant/hemodialysis patients, and infants born to mothers with hepatitis B.
• Mandatory blood donor screening has reduced transfusion-associated hepatitis cases.
• Other modes of transmission exist with HBsAg detected in saliva, nasopharyngeal washings, semen, menstrual fluid, vaginal secretions, as well as in blood.
• Transmission occurs from carriers to close contacts by oral or sexual routes and other close exposures.
• Fecal-oral transmission has not been documented.
• All bodily fluids from infected patients are considered infectious.
• Subclinical infections are common and pose a hazard to hospital personnel, as healthcare workers have a higher incidence of hepatitis with an incubation period of 50-180 days (60-90 average).
• Incubation varies with viral load and administration route, being longer with lower doses or non-percutaneous routes.

Hepatitis B Pathogenesis

• The outcome varies after infection with possibilities consisting of: complete recovery, chronic hepatitis, or, rarely, death.
• 65-80% of infections in adults are inapparent, with 90-95% recovering but, 80-95% of infants/young children develop into chronic carriers and remain serum positive for HBsAg.
• Chronic carriers of HBV are often asymptomatic for many years with those at high risk may eventually develop hepatocellular carcinoma.
• Hepatocellular carcinoma (HCC) is a major cause of death.
• 80% of primary HCCs occur in HBV-infected people.
• HBV being a DNA virus, results in viral genome integration into the host's chromosome which potentially causes mutation and cell growth change.

Hepatitis B Diagnosis

• Diagnosis involves liver function tests with liver biopsy.
• PCR detects viral DNA.
• ELISA detects viral antigens and antibodies.
• HBV DNA and HBeAg are present in the viremic stage during the incubation period when communicability is highest.
• HBsAg is detectable for 2-6 weeks and persists with active disease.
• HBsAg disappearance indicates recovery.
• High Anti-HBc IgM indicates onset of clinical illness (a marker against the HBV internal core component and its appearance in serum indicates replication).
• HBV chronic carriers show HBsAg persistence for > 6 months with HBeAg or anti-HBe detected.
• HBsAg can persist for years after the loss of HBeAg.
• Low levels Anti-HBc IgM exist in the blood of carriers of HBsAg.

Hepatitis B - Treatment:

• 95% of acute cases require no treatment, as they are self-limited.
• Chronic cases are treated to reduce the risk of progressive liver disease and long-term complications.
• Pegylated interferon alfa-2a, entecavir, and tenofovir are first-line therapies; these are the different types of HBV polymerase inhibitors
• Telbivudine, a cytosine nucleoside analogue, is a second-line therapy and inhibitor of HBV DNA polymerase.
• Lamivudine and adefovir are nucleoside analog viral polymerase inhibitors that are third-line agents.

Hepatitis B - Prevention:

• General measures consist of the screening of blood before transfusion and infection control practices.
• Use of recombinant HBsAg synthesized by yeast in active immunization.
• Egypt applied an HBV vaccination program in 1992 with a schedule of 2, 4 and 6 months.
• For non-vaccinated adults, 3 IM doses with 6-month intervals are needed.
• Immunosuppressed people respond to vaccination at a lower rate compared to healthy people.
• Passive immunization uses Hepatitis B Immune Globulin, shown to give a protective effect if give it soon after exposure.
• HBIG is not recommended for pre-exposure due to the HBV vaccine availability.
• Individuals exposed to HBV through percutaneous or mucosal routes should receive HBIG and HBsAg vaccine simultaneously at different injection sites with the recommendation including Infants born to infected mothers and people accidentally exposed to HBV-contaminated blood or needles.

Hepatitis C

• First discovered in 1988, Hepatitis C is caused by NANB and is associated with blood transfusions.
• According to the WHO, 1% of the world's population is infected with hepatitis C, leading to cirrhosis and/or liver cancer for million of people.
• According to a 2015 Egyptian Health Issues Survey, 7% of the population between 15 and 59 years old were infected with hepatitis which is higher than the global average.

Hepatitis C - Transmission

• Percutaneous exposure to blood is the primary transmission method.
• 80% results from IV drug use.
• Also from hemophiliacs treated with clotting products (before 1987), recipients of transfusions from HCV-positive donors, chronic hemodialysis, and healthcare workers.
• Less common transmission from mother to infant (3-10%) when pregnant and higher rate with higher viral load or co-infection of HIV.
• No transmission through breasfeeding.
• Transmission has been found in saliva from more than 1/3 of patients with HCV and HIV co-infections.
• Incubation is 6-7 weeks with 90% of patients showing as anti-HCV-positive within 5 months.

Hepatitis C - Pathogenesis:

• Viral replication occurs in hepatocytes.
• Liver cell destruction may arise due to viral gene products and the immune response.
• Most infections are subclinical with 25% presenting as jaundice hepatitis.
• Significant amount develop chronic hepatitis and cirrhosis.
• A percentage of people (5-25%) develop hepatocellular carcinoma 15-60 years after initial infection.
• 40% of chronic liver disaeses are HCV related.
• End-stage liver disease from HCV is the most common reason for liver transplants.
• There are 4 pre-domiant stereotypes: 1, 2, 3 and 4.
• Type 4 has the highest rate of occurrence leading to chronic infection.

Hepatitis C - Diagnosis

• Serologic assays can diagnose HCV infection.
• Enzyme immunoassays identify antibodies to HCV but cannot differentiate infections (acute, chronic, resolved).
• A delay in appearance Anti-HCV may take 3-6 months for results to come back.
• Nucleic acid tests (e.g. RT-PCR) identifies HCV RNA circulating with test helpful for early cases before results from serology.
• Used to reveal active viral replication (serum for therapy), follow up treatment loads, and genotyping.

Hepatitis C - Treatment

• Classic treatment involves interferon alpha in combination with antiviral ribavirin.
• Several conditions affect overall response, and treatment is based on viral genotype and patient age, viral load, and degree of liver fibrosis.
• Genotypes 2 and 3 show higher rates 75-80% as opposed to type 1 (30-35%). Subtype 4a results in poor treatment response.
• Treatment duration is about 24-28 weeks depending on viral Genotype.
• Current: Direct-acting antiviral drug (DAADs) like: Sofosbuvir, nucleotide analog HCV/ Simepravir HCV protease inhibitor/Daclatasvir which causes RNA replication.
• Current drugs show less toxicity greater efficacy, are Interferon-free and better cure rates.

Hepatitis C - Prevention

• There is no effective vaccine available yet .
• Screening is performed on HCV in blood, plasma, and tissue.
• Practices are being implemented with regards to infection control and and education across setting.
• Washing of contact site and follow up is high recommended .

Hepatitis D (Delta Agent) Epidemiology

• HDV occurs only with HBV co-infection and is more common in Mediterranean countries.
• Transmitted like HBV, though without sexual transmission.
• HDV presence is more severe in liver damage.

Hepatitis D (Delta Agent) Diagnosis:

• Diagnosis by Anti- HDV antibodies through (ELISA) and PCR.

Hepatitis D (Delta Agent) Treatment:

• With no treatment for HDV;Vaccination for HBV can prevent HDV though Hepatitis B carriers remains susceptible to it.

Hepatitis E

• HEV is waterborne, RNA virus without a membrane mainly transferred enterically and waterborne in countries with less economic progression.
• Presence comes through RT-PCR and detection of antibody.
• Symptoms are equal to that of Hep A with not progressing.
• There is no vaccine or treatment for HEV.

Types of Hepatitis Comparison

• Hepatitis viruses can be differentiated by virus type (ssRNA or dsDNA), prevalence, chronic infection, oncogenicity, source, and transmission mode.

Retroviruses

• Retroviruses use reverse transcriptase to convert single-stranded RNA into double-stranded DNA.
• Information transfers in the opposite DNA form and retro translating in backwards formation

Retroviruses – Types of Human Lymphocytes

• Two genera are lentivirus, including Human immunodeficiency types (HIV 1 ) and Human T cell Lymphocytes ( HTLV BLV )

HIV - Characteristics

• Enveloped virus with 2 single strands of RNA
• Enzymes: Reverse, transcriptase, integrate, pro-tease

HIV – Steps of replication

• Bonding of host and T-4 lymphocytes.
• Reverse transcribe the Viral RNA.
• Insertion of the Viral DNA.
• Can no be cured unless replication is stopped.
• The Viral RNA will act as replica for viral particles
• Assembly of RNA then excepts Cytolysis

HIV

• HIV causes immune deficiency Syndrome (AIDS)
• Can be found as central Aftica
• Transferred through Sexual, percutaneous & From mother to fetus. Transferred from Blood & Semen

HIV - Transmission,

• Occurs via, present infection, diseases of syphilis increases.
• Found in Blood and V againal secretions.
• Can be as much one hundred if diseases appear
• Can come from blood and or clotting factors 15- 40% in new borns , birth processes, from the absence of infection 30 % with 70 % during deliver and high maternal loads. Low chance of health workers from a needle contamination risk is less or more mucous blood 0.09

HIV - Not Transmitted

• Not transferred by casual touch .

HIV - Pathogenesis

• Has 4 Stages - Primary, Symptomatic, Asymptomatic, AIDS stages

HIV - Pathogenesis: Primary stage

• Occurs from one to 6 weeks during infection.
• Very unnoticeable for infecting and may cause some infection.

HIV - Pathogenesis: Asymptomatic stage

• Can last for a decade that does not show infection.
• Will show a slight low level can be swapped or can test positive the blood

HIV - Pathogenesis: Asymptomatic stage

• This cannot replace the infected cells
• As infection spread increases, symptoms show.
• And immune systems decrease of other effects.

HIV - Pathogenesis: AIDS Stage

• The immune system weakens.
• The infections and illnesses gets severe

HIV - Pathogenesis: Virus functions

• It harms T4 Helper cells.
• Attachment of viral levels create expression of fusion into cell with suppression of overall immune functions.

HIV - Diagnosis

• Can be detected earlier though very sensitivity
• Can detect low viral levels, appropriate therapy
• 25 day window

HIV - Treatment

• Strategy multiple drug treatment can cause issues as a high rate of effects.
• High rate of a recombination. _ Strategy drugs can work but need to be multiple due high rates of effect , combination , etc

HIV - Prevention :

• HAART & NRTIs, can be infected or protein copies.
• Pls can copy itself.
• Block cd4 sells or integates.
• HAART is discontinued and rebounds to cause treatment of long cells.
• High doses can prevent transision from breastfeeding etc