Tema 4

Hepatitis A Overview

Introduction to Hepatitis A

• The hepatitis A virus belongs to the Picornaviridae family and is transmitted via the fecal-oral route, similar to coronaviruses. It contains RNA as its genetic material.

• Hepatitis A infection results in an acute illness that does not become chronic. Its primary transmission occurs through contaminated food and water.

Clinical Presentation

• Typical cases involve children presenting with fever, asthenia, anorexia, and right upper quadrant pain; jaundice appears later in the course of illness.

• In 90% of pediatric cases, symptoms are nonspecific and most children do not exhibit jaundice during infection.

Adult vs. Pediatric Cases

• Adults tend to experience more severe symptoms and complications compared to children who usually have a milder course of illness.

Serological Markers and Diagnosis

• During the prodromal phase, viremia leads to symptoms like fever and anorexia; transaminases elevate predominantly in ALT (TGP).

• Diagnosis involves measuring transaminases where the TGP/TGO ratio is typically less than one due to higher elevation of TGP.

Prognosis and Treatment

• The prognosis is assessed using prothrombin time (TP), which indicates early liver failure; complications are rare but can occur in less than 1% of cases.

• Treatment is symptomatic with no specific antiviral therapy for acute hepatitis A; prevention includes vaccination starting at one year of age.

Hepatitis E Overview

Introduction to Hepatitis E

• The hepatitis E virus belongs to the Hepeviridae family, primarily causing acute infections but can rarely lead to chronic infections in immunocompromised individuals.

Transmission Routes

• Similar to hepatitis A, hepatitis E mainly spreads through fecal oral routes but also has vertical transmission potential.

Clinical Features

• The incubation period ranges from 2 to 8 weeks, with adults commonly presenting with symptoms such as anorexia, asthenia, and fever.

Hepatitis Overview and Key Insights

Understanding Hepatitis E in Pregnant Women

• Hepatitis E is particularly dangerous for pregnant women, with complications leading to fulminant liver failure in up to 20% of cases. Remember "E" for "Embarazada" (pregnant) when considering risks.

Diagnosis and Treatment of Hepatitis A and E

• The diagnostic approach for hepatitis A and E includes observing biremia, fecal excretion, elevated transaminases (predominantly TGP), and the presence of IgM antibodies against hepatitis C virus during acute phases. Treatment remains symptomatic as there is no vaccine available for hepatitis E.

Transitioning to Hepatitis B: Characteristics

• Hepatitis B belongs to the family of hepadnaviruses, characterized as an ADN virus that can lead to chronic infection in about 10% of cases. Its incubation period ranges from 1 to 6 months. The viral particle is known as the Dane particle.

Serological Markers in Hepatitis B

• Important serological markers include:

• Surface antigen (also called Australian antigen) indicating active infection.

• Antigen E indicates viral replication.

• Core antigen which is not measured directly; instead, we measure antibodies against it. Understanding these components aids diagnosis significantly.

Transmission Routes and Prognosis of Hepatitis B

• Major transmission routes include sexual contact, parenteral exposure (blood transfusions, needle stick injuries), and vertical transmission (from mother to child). Early infection increases the risk of chronic disease progression leading potentially to cirrhosis or hepatocellular carcinoma later on. Thus, early age at infection correlates with worse prognosis.

Acute vs Chronic Infection Dynamics

• Acute hepatitis B infections have a high recovery rate (90-95%), but about 5-10% may progress to chronicity with serious outcomes like fulminant hepatic failure (<1%). Chronic infections can evolve into cirrhosis in approximately 15-20% of patients, highlighting the importance of monitoring serological markers throughout the course of illness.

Understanding Hepatitis: Acute vs. Chronic

Overview of Hepatitis Manifestations

• The initial marker for hepatitis is identified, particularly in acute infections, which present symptoms such as fever, right upper quadrant pain, jaundice, and asthenia.

• Chronic infection is defined as lasting more than six months; most patients are asymptomatic but may exhibit nonspecific symptoms or liver failure with coagulopathies and encephalopathy.

Differentiating Acute and Chronic Infections

• The presence of the anti-core antibody (anticore) distinguishes between acute and chronic infections; it’s crucial to understand that "anti" refers to antibodies while "Ag" denotes antigens.

• IgM against the core indicates an acute infection, whereas IgG signifies a chronic infection. This distinction is vital for diagnosis.

Role of Surface Antigen

• If only the surface antigen is positive for less than six months, it indicates an acute infection; if positive for more than six months, it suggests a chronic condition.

• The E antigen indicates viral replication; its positivity during acute infection shows active virus multiplication.

Serological Markers and Their Implications

• A positive E antigen at the onset of acute infection signals active replication; its decline alongside rising anti-E antibodies indicates that the virus is no longer replicating.

• Understanding serological markers helps track disease progression from active to inactive states.

Extrahepatic Manifestations of Hepatitis B

• Chronic hepatitis B can lead to specific pathological patterns like "ground-glass hepatocytes" and has various extrahepatic manifestations including chronic polyarthritis resembling rheumatoid arthritis.

• Rheumatologists often test for hepatitis B serology when diagnosing chronic polyarthritis due to its association with conditions like polyarteritis nodosa.

Importance of Accurate Diagnosis

• The first serological marker indicating hepatitis presence is the surface antigen. However, differentiating between acute and chronic forms relies heavily on anticore testing.

• Recognizing whether a patient has an active or inactive state involves monitoring E antigen levels—its positivity reflects ongoing viral replication.

This structured overview provides clarity on key concepts related to hepatitis diagnosis and management based on serological markers.

Understanding Hepatitis Markers and Their Implications

Overview of Hepatitis Infection States

• The presence of antigen E indicates active hepatitis, which can be either acute or chronic. Chronic hepatitis may transition to a state where antibodies appear instead of antigens.

• The emergence of antibodies against antigen E signifies that the virus is no longer replicating, indicating an inactive infection state.

Interpretation of Serological Markers

• Key markers include surface antigens for infection status and core antibodies to differentiate between acute and chronic infections. IgM against core is the first immune response marker.

• Distinction between serological markers (surface antigen vs. immune response antibody) is crucial; IgM against core indicates acute hepatitis.

Replication and Infectivity Indicators

• Antigen E serves as a qualitative marker for replication and infectivity, while PCR provides a more specific quantitative measure.

Determining Health Status in Patients

• A patient is considered healthy if they have antibodies against the surface antigen, indicating protection through vaccination or recovery from infection.

• Positive results for surface antigen antibodies suggest either recent recovery from infection or successful vaccination.

Differentiating Between Vaccination and Recovery

• In cases of past infections, only surface antigen antibodies will be positive after a long time since recovery; other markers will be negative.

• Recent recoveries show both surface antigen antibodies and positive IgG against core, indicating recent healing from an infection.

Complications in Marker Interpretation

• When both surface antigens and their corresponding antibodies are present, it indicates a convalescence period where the patient is recovering but still has detectable viral markers.

• This dual positivity can confuse diagnosis; understanding this phase as convalescence helps clarify patient health status.

Window Period Considerations

• If the surface antigen is negative but IgM against core is positive, it suggests a window period where the infection might not yet be fully detectable despite active immune response.

Understanding Hepatitis B Markers and Treatment Protocols

Key Concepts in Hepatitis B Diagnosis

• The IgM antibody against core antigen (IgM anti-Cor) is the first detectable marker in the immune response to hepatitis B, indicating an active infection.

• A negative surface antigen (antigen E) suggests no viral replication; however, a high PCR result can indicate otherwise, leading to potential discordance between qualitative and quantitative markers.

• The discrepancy between antigen E (qualitative marker) and PCR (quantitative marker) can signify a precore mutant, which has a poor prognosis.

Importance of Accurate Interpretation

• It is crucial to trust the PCR results over qualitative markers like antigen E when assessing viral replication status.

• Memorizing key data points regarding hepatitis B interpretation is essential for accurate diagnosis and treatment planning.

Treatment Approaches for Hepatitis B

• Acute infections typically require symptomatic management only, while chronic infections necessitate antiviral treatments.

• Differentiation among various clinical scenarios based on criteria such as cirrhosis presence, transaminase levels, and viral load is vital for treatment decisions.

Clinical Scenarios for Treatment Decisions

• Seven distinct clinical scenarios are outlined based on liver health indicators: cirrhosis presence, transaminase levels, and viral load.

• Scenario 1: Patient with chronic hepatitis B and cirrhosis.

• Scenario 2: No cirrhosis but elevated transaminases and high viral load.

• Scenario 3: Mildly elevated transaminases with also elevated viral load.

Criteria for Initiating Antiviral Therapy

• Patients over 30 years old with normal transaminases but positive viral markers may still require treatment due to active virus replication.

• Treatment should be initiated if there are signs of active disease indicated by high transaminases or significant viral loads regardless of age or other factors.

Summary of Non-Treatment Scenarios

• Scenarios where patients have normal transaminases alongside low or undetectable viral loads do not warrant immediate treatment initiation.

• Emphasis on monitoring patients under these conditions until further progression occurs.

This structured approach provides clarity on diagnosing and managing hepatitis B effectively while highlighting critical insights from the discussion.

Understanding Hepatitis Treatment and Prognosis

Importance of Transaminases in Treatment Response

• High transaminase levels indicate that a patient is likely to respond well to antiviral treatment. This is crucial for determining the initiation of therapy.

• Normal transaminase levels suggest a poor prognosis, indicating that the patient may not respond effectively to treatment. Thus, elevated transaminases are seen as a positive sign.

Factors Influencing Prognosis

• A low viral load before treatment is favorable, while infections acquired horizontally (as opposed to vertically) have better outcomes; younger patients tend to have worse prognoses.

• Key factors for good prognosis include active hepatitis without co-infections like HIV or hepatitis delta, particularly in women. Tenofovir is the preferred antiviral for chronic hepatitis B management with high viral loads.

Antiviral Treatments and Monitoring

• Tenofovir can be used safely in pregnant women infected with hepatitis B unless there are contraindications such as renal impairment or osteoporosis; in these cases, entecavir is recommended instead.

• Treatment response is monitored by normalizing transaminases and observing seroconversion of antigen E within three months, alongside low viral load via PCR testing. This indicates effective treatment response.

Vaccination and Postnatal Care

• Vaccination against hepatitis B is essential for newborns, especially those born to mothers with active infections; they should receive both the vaccine and gamma globulin for protection against infection.

• Newborn care includes administering gamma globulin along with vaccination if the mother tests positive for surface antigen of hepatitis B during pregnancy. This dual approach enhances immunity in infants at risk.

Hepatitis C: Risks and Diagnosis

Characteristics of Hepatitis C

• Hepatitis C belongs to the flavivirus family and has an RNA genome; it has a high chronicity rate of up to 85%, making it more likely than other types to lead to long-term infection after exposure.

• The incubation period ranges from two weeks to six months, primarily transmitted through parenteral routes such as intravenous drug use or blood transfusions prior to screening measures implemented post-2000.

Transmission Risks

• Parenteral transmission poses significant risks during needle-stick injuries; healthcare workers should be particularly cautious about potential exposure due to higher chronicity rates associated with hepatitis C compared to other viruses like HIV or HBV following such incidents.

• In situations involving tattoos or piercings where equipment may not be sterile, there’s also an increased risk of contracting hepatitis C due to its primary transmission route being parenteral rather than sexual or vertical transmission methods typically associated with other viruses like HIV or HBV.

Diagnostic Testing

• Diagnosis involves testing antibodies against hepatitis C (anti-HCV) through ISA and confirming viral presence via PCR; both tests must align positively for confirmation of infection status.

• If anti-HCV is positive but PCR negative, this indicates a false positive requiring retesting.

• Conversely, if anti-HCV is negative but PCR shows positivity, this suggests either a window period or immunosuppression affecting antibody production (e.g., co-infection scenarios).

Hepatitis C: Understanding Complications and Treatment

Overview of Hepatitis C Complications

• The majority (80%) of hepatitis C cases are asymptomatic, highlighting the importance of screening for at-risk patients starting at age 40.

• Extrahepatic complications include membranoproliferative glomerulonephritis, which can lead to nephritic syndrome, and various vasculitis conditions associated with hepatitis C.

• Chronic infection is linked to interface hepatitis in pathological studies; favorable prognostic factors include genotypes two and three.

Prognostic Factors in Hepatitis C

• Good prognosis indicators include low viral load, absence of cirrhosis, younger age, and positive response to antiviral treatment.

• The recommended pangenotypic treatment regimen consists of sofosbuvir combined with velpatasvir due to its broad genotype coverage.

Historical Treatment Approaches

• Previously used treatments included interferon alpha plus ribavirin; duration varied based on genotype prognosis—six months for good prognostic genotypes (2 and 3), one year for poor ones (1 and 4).

Delta Virus: Characteristics and Infection Types

Nature of the Delta Virus

• The delta virus is an incomplete virus that requires co-infection with hepatitis B for replication; it contains defective RNA material.

Transmission Routes

• Similar transmission routes as hepatitis B: sexual contact, parenteral exposure, and vertical transmission from mother to child.

Coinfection vs. Superinfection

• Coinfection occurs when a patient with acute hepatitis B becomes infected with the delta virus during the acute phase; incubation lasts 1 to 6 months.

• Serological markers indicate coinfection through positive surface antigen for hepatitis B and IgM against core protein alongside delta antibodies.

Differentiating Between Coinfection and Superinfection

Key Differences in Infection Types

• Superinfection involves a chronic hepatitis B patient who subsequently contracts the delta virus; this form has a shorter incubation period (2 to 8 weeks).

Serological Markers Interpretation

• In superinfection cases, serology shows positive surface antigen but negative IgM against core protein while still showing antibodies against the delta virus.

Importance of Core Antibody Testing

• The presence or absence of IgM against core protein differentiates between coinfection (positive IgM indicates recent infection) and superinfection.

Understanding Coinfection and Superinfection

Key Concepts in Serological Markers

• The presence of IgM against the core indicates a coinfection, while a negative IgM with a positive IgG suggests superinfection. This distinction is crucial for diagnosis.

• The core antibody (anticore) serves as a key differentiator between the states of coinfection and superinfection, highlighting its importance in serological testing.

• Treatment for delta virus infections involves the use of interferon alpha, emphasizing its role in managing viral infections effectively.

• Emphasis on reviewing serological markers is essential; practitioners are encouraged to self-evaluate and familiarize themselves with these markers to enhance their understanding and diagnostic skills.

• Continuous practice and review of serological markers are recommended to ensure proficiency in identifying different infection states.