Viral Hepatitides

Viral Hepatitides

1º and 2º Hepatotropic Viruses

Primary Hepatotropic Viruses

  • Definition: Primary hepatotropic viruses directly target and infect the liver.

  • Hepatitis A Virus (HAV):

    • Causes acute, self-limiting liver infection.

  • Hepatitis B Virus (HBV):

    • Can cause both acute and chronic liver disease.

  • Hepatitis C Virus (HCV):

    • Often leads to chronic liver disease, resulting in complications such as cirrhosis and liver cancer.

  • Hepatitis D Virus (HDV):

    • A type of hepatitis that can only infect individuals already infected with HBV.

  • Hepatitis E Virus (HEV):

    • Causes acute infection similar to HAV.

Secondary Hepatotropic Viruses

  • Definition: Secondary hepatotropic viruses can also cause liver damage but are not primarily liver-targeting.

  • Cytomegalovirus (CMV):

    • A herpesvirus associated with liver injury, particularly in immunocompromised individuals.

  • Epstein-Barr Virus (EBV):

    • Another herpesvirus that may lead to liver inflammation.

  • Herpes Simplex Virus (HSV):

    • Primarily known for cold sores but can affect the liver, especially in newborns and immunocompromised patients.

  • Varicella-Zoster Virus (VZV):

    • Virus causing chickenpox and shingles can sometimes lead to liver inflammation.

  • Hepatitis G Virus (HGV):

    • Officially known as human pegivirus (HPgV-1) or GB virus C (GBV-C). It replicates primarily in the hematopoietic system, particularly in lymphocytes and bone marrow cells.

  • Other Viruses:

    • Additional viruses like adenovirus, coxsackievirus, and parvovirus B19 may also cause liver damage.

Hepatitis A

Etiology

  • Causative Agent: Hepatitis A Virus (HAV).

  • Characteristics of HAV:

    • A small RNA virus measuring 27 nm with no envelope.

    • Replicates in the cytoplasm of infected hepatocytes.

Epidemiology

  • Occurrence: Can present sporadically, endemically, or in epidemic forms.

  • Incubation Period: Ranges from 15 to 50 days.

  • Global Spread: Present worldwide, with higher prevalence in underdeveloped countries.

  • Transmission:

    • Fecal-oral infection from individuals with hepatitis A who excrete the virus in stool, 1-2 weeks before and after onset of symptoms.

  • Transmission Routes:

    • Contaminated water, food, dirty hands, and oral-anal sexual contact.

  • Epidemic Nature: Often arises from hydric or alimentary sources; sporadic cases can occur among household contacts.

  • Seasonality: Highest incidence observed in November and December.

Pathogenesis

  1. Absorption: Virus is absorbed from the digestive tract.

  2. Blood Circulation: The virus travels through the bloodstream to the liver.

  3. Reproduction: The virus reproduces in the liver.

  4. Damage Mechanisms:

    • Cytopathogenic effects (less significant).

    • Host immune responses greatly contribute to liver damage.

Clinical Presentation

  • Generally milder than hepatitis B.

  • Seroconversion: Occurs in one-third of HAV-infected individuals without clinical signs of liver inflammation.

  • Stages of Acute Viral Hepatitis A:

    1. Prodromal (Preicteric):

    • Duration: 3-10 days (up to 3 weeks).

    • Symptoms include malaise, sneezing, sore throat, headache, muscle and joint pain, diarrhea, and fever.

    • Also includes pain in the right rib cage and dyspeptic symptoms (nausea, vomiting).

    1. Icteric Stage:

    • Duration: About 4 weeks.

    • Symptoms: Jaundice, dark urine, light-colored stool, and liver pain.

    • Physical examination may show enlarged and sensitive liver in 80% of patients; 20% may have an enlarged spleen, and lymph nodes can be swollen.

    1. Convalescence Stage:

    • Duration: 2-12 weeks.

    • Recovery occurs; the liver returns to normal size, but fatigue may persist.

    • Clinical and laboratory recovery is typically completed in 1-2 months.

Atypical Forms

  • Subclinical (Asymptomatic): Particularly in children, with elevated transaminases.

  • Anicteric: Symptoms similar to icteric but without jaundice.

  • Cholestatic: Elevated bilirubin and bile duct enzyme levels despite mild symptoms, lasting from 3 to 8 months.

  • Prolonged: Exceeding three months in duration.

  • Recurring/Biphasic: Periods of symptoms followed by relief.

  • Fulminant Hepatitis: Extremely rare (0.1% likelihood). Complications include autoimmune hepatitis.

Diagnosis

  • Evaluation: Anamnesis, epidemiological survey, and laboratory results.

  • Biochemical Analysis:

    • Elevated AST, ALT at least 10 times above normal.

    • ALT often exceeds AST.

    • Hyperbilirubinemia, mainly conjugated bilirubin.

    • Increased urine urobilinogen; decreased stool bile salts.

  • Coagulation Disorders: Rarely observed.

  • Blood Count: May reveal leukopenia with mild lymphocytosis.

  • Virological Analyses:

    • ELISA tests for anti HAV IgM and IgG antibodies.

Differential Diagnosis

  • Primary hepatotropic causes: HAV, HBV, HCV, HDV, HEV.

  • Secondary hepatotropic causes: EBV, CNV, Coxsackie B virus, HSV, Adenovirus, Yellow fever, and various other viruses.

  • Conditions from icterus syndrome: Leptospirosis, NASH, granulomatous hepatitis, autoimmune and metabolic hepatitis, toxic hepatitis, ischemic hepatitis, obstructive jaundice, and HELP syndrome during pregnancy.

Treatment

  • Focus on symptomatic therapy and hygienic-dietary regimen.

  • Recommendations:

    • Bed rest, infusion of 10% glucose, light, carbohydrate-rich diet.

    • Avoid fatty foods and alcohol.

  • Outcomes:

    • Healing typically occurs within 1-2 months.

    • Fulminant hepatitis occurs in less than 0.1% of cases.

    • No chronic form; solid, lifelong immunity develops.

Hepatitis E

  • Common Features with HAV: Similar in that it is a small virus, lacks an envelope, is shed in stool, and does not lead to chronic disease.

  • Epidemiology: Incubation period lasts from 15 to 60 days.

Hepatitis B – Acute and Chronic

Etiology

  • Causative Agent: Small DNA virus, approximately 42 nm.

  • Resistance: Highly resistant in the external environment.

  • Structure:

    • Outer Envelope: Composed of lipoprotein coat with HBsAg (also present in different forms: sphere and tubular).

    • Inner Core (Nucleocapsid):

    • Contains 2 antigens: HBcAg (Core antigen) and HBeAg (Envelope antigen).

    • Contains HBV DNA as the viral genome alongside DNA polymerase (reverse transcriptase) and protein kinase.

Epidemiology

  • Incubation Period: Ranges from 30 to 160 days, averaging 60 to 90 days.

  • Sources of Infection: Individuals suffering from acute or chronic infections or asymptomatic carriers.

  • Transmission Routes:

    • Primarily via blood, sexual contact, or perinatal transmission. Rarely via oral transmission.

  • Chronicity Rates:

    • Acute HBV may transition to chronic in 1-5% of infected adults, 90% in infants infected at birth, and 50% in children up to age 5.

Pathogenesis

  • Cytopathogenic Nature: HBV does not directly cause cytopathic effects in hepatocytes.

  • Hepatitis Pathogenesis: Results from immune lysis of infected hepatocytes.

  • Immune Response: Quality and strength determine disease outcome. Key roles include:

    • Cellular Immune Response: Cytotoxic T lymphocytes (CTL) recognize and lyse infected cells, interacting with processed viral antigens on HLA class I.

    • Humoral Response: Antibodies neutralize and remove viral particles. Notable roles in extrahepatic manifestations.

Immune Dynamics

  • Key Players: CTL, CD4 helper T cells, and B lymphocytes.

  • Strong Polyclonal Response: Seen in patients clearing acute HBV.

  • Weak Response: Associated with the development of chronic HBV infection.

  • Antibody Production: Against HBsAg and HBcAg; the latter does not neutralize the virus but contributes to immune response complexity.

Clinical Presentation of Acute Hepatitis B

  • Symptoms analogous to those in hepatitis A but may include:

    1. Prodromal (Preicteric) Stage:

    • Gradual onset; can experience a serum sickness-like syndrome (fatigue, arthralgia, rash).

    1. Icteric Stage: Jaundice, liver pain, and symptoms described above.

    2. Convalescence Stage: Clinical recovery might last from 2-6 months, with atypical forms such as anicteric, prolonged, and relapsing present.

Fulminant Hepatitis

  • Description: Most severe form of acute hepatitis, leading to rapid impairment of liver function.

  • Manifestations: Severe jaundice, encephalopathy, coagulopathy, and systemic organ dysfunction.

  • Characteristic Symptoms: Persistence of signs from the preicteric stage, increasing confusion, and liver shrinkage.

  • Consequences: Elevated ammonia leading to potential brain dysfunction and metabolic disturbances.

Diagnosis

  • Tests: Virological diagnosis through assessing HBsAg and anti HBc IgM for acute cases.

Treatment

  • Antivirals: Lamivudine and tenofovir.

  • Supportive measures: Similar to those for hepatitis A, including dietary recommendations and symptomatic treatment.

  • Severe Cases: Requires management of hepatic encephalopathy and potential liver transplantation.

Outcome

  • Typical recovery in 2-4 months; chronic hepatitis may develop in 5-10% of cases with higher likelihood in specific demographics.

  • Liver cirrhosis can socially progress post-fulminant form.

Prevention

  • Hygiene: General and personal hygiene measures.

  • Medical Practices: Use of disposable needles and sterilization regulations.

  • Vaccination: Critical in preventing transmission, especially perinatally from HBsAg positive mothers.

Chronic Hepatitis B (CHB)

  • Definition: Persistent inflammatory reaction in liver tissue lasting at least 6 months, often due to weak immune response.

  • Clinical Presentation: Typically subclinical; symptoms are generally fatigue, weakness, and discomfort under the right rib cage.

  • Diagnosis: Often incidental during routine examinations.

Stages of CHB

  1. Immunotolerant Phase: High HBV DNA, normal transaminases.

  2. Immunoelimination Phase: Elevated transaminases, potential for seroconversion.

  3. Inactive Phase: Low HBV DNA, normal transaminases.

  4. Reactive Phase: Elevated HBV DNA and transaminase levels.

Long-term Concerns

  • Cures: No complete cure exists; cccHBV DNA persists, allowing for potential reactivation.

  • Oncogenesis Risk: Integration of HBV genome into host DNA can lead to hepatocellular carcinoma.

Complications

  • Liver fibrosis and cirrhosis; decompensated cirrhosis can develop.

Therapy

  • Focus on immunoactive and reactivation phases; not required in tolerant or inactive phases.

  • Goals of Treatment:

    • Suppression of HBV replication, normalization of transaminases, and disappearance of HBeAg.

  • Medications: Include PEG IFN, nucleoside/nucleotide analogues (lamivudine, tenofovir).

Hepatitis C (HCV)

Etiology

  • Characteristics: Spherical particle (55 nm) from the Flaviviridae family.

  • Structure: Single-stranded HCV RNA core with lipoprotein coat (E1 and E2 glycoproteins).

  • Genome: Encodes structural (core protein) and non-structural proteins crucial for virus replication.

Epidemiology

  • Infection Source: Individuals with acute or chronic HCV.

  • Chronicity Rate: Approximately 80% will develop chronic form.

  • Transmission Methods: Parenteral (blood transfusions), IV drug use, and less commonly sexual or perinatal routes.

Pathogenesis

  • Mechanism: HCV does not directly cause cytotoxic effects but uses immune system response leading to liver damage.

  • T lymphocytes mediate the immune response but may be insufficient to eradicate the virus.

Acute Hepatitis C

  • Presentation: 85% asymptomatic; can present as mild clinical picture.

  • Progression: 20-50% may recover spontaneously; approximately 50-85% progress to a chronic form.

Diagnosis

  • Tests: Detection of anti-HCV antibodies and HCV RNA via PCR.

Prevention

  • Absence of a vaccine; testing recommended for those exposed.

Chronic Hepatitis C

  • Picture: Often oligosymptomatic until cirrhosis or carcinoma develops.

  • Extrahepatic Manifestations: Vasculitis, nephropathy, and other complications may occur.

  • Therapeutics: Direct antiviral medications such as sofosbuvir combinations.

Hepatitis D

  • Nature: Defective virus that requires HBV for replication.

  • Diagnosis: Identified via IgM anti-HDV antibodies in HBsAg positive individuals.

  • Clinical Importance: Worsens outcomes of HBV infection and contributes to liver damage.