1. Hepatitis

2. Types of liver infection:
Hepatitis.
liver abscess: collection of pus within the liver.
Parasitic infection.
Hepatitis is the inflammation of liver caused by immune response against liver parenchyma induced by viral infections, or intracellular pathogens that survive in Kupffer cells causing granulomatous infections (typhoid fever, brucellosis, Q fever, T.B).

3. Viral causative agents of hepatitis can be:
Professional-hepatitis viruses: Hepatitis A,B,C,D, and E viruses: strong tropism to hepatocyte.
Non-professional viruses: Viruses that cause extra-hepatic diseases: Yellow fever viruses, E.B virus secondary to I.M, CMV, adenoviruses, Herpes simplex viruses, VZV…..

4. Hepatitis Viruses: Hepatitis A, B, C, D, and E:
Type
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Mode of
Transmission
Fecal-Oral*
Bloodborne
Sexual
Vertical
Blood borne
(depend on HBV)
Super or co infection
Classification
Picornaviri-dae. Linear SS-RNA
Hepadnaviriae
Circular DS DNA R.T enzyme
Flaviviridae
Linear SS-RNA
Deltaviridae
Circular SS RNA
Calicivirid-ae
Linear SS- RNA
Incubation
2—6 weeks
2 –6 months
2 weeks- 6 months
days
21-42 days
Chronic infection
NO.
YES (10%)
YES (60 -80%)
YES
Outcomes
of Chronic Infection NO
Cirrhosis or Hepatocellular Carcinoma N
* Can be transmitted by anal-oral sex and by blood during the brief bacteremia

5. HBV infection prevalence
350 million are persistently infected by HBV
Low < 2%
Low intermediate 2-4%
High intermediate 5-7%
High >7%

6. Hepatitis B virus: Pathogenesis:
Virus infect the liver cells and multiply inside them causing lysis and necrosis in the hepatocyte causing hepatitis.
→ interferon induce by infected cells →MHC-1 expression on the hepatocyte with the viral antigens.
→ cell mediated immunity (CD-8 & NK& macrophages) eliminate and destroy the viral infected hepatocytes.
Also Ag-Ab. Complex formed which may cause type III immune complex disorder.

7. Clinical presentation of hepatitis B infection:
Acute infection period:
A- Pre-icteric phase: mild fever, loss of appetite, myalgia, and fatigue.
B- Icteric acute phase: (1-2 months): Jaundice (yellowish coloration of mucous membrane, conjunctivae, and skin), enlarged and tender liver.
C- Fulminant hepatitis: (in 1-2% of patients): sever necrosis of liver in icteric phase; encephalopathy and lethal in 8% of cases (HEV in pregnancy or HBV-HDV coinfection) .

8. Complications:
Chronic carrier (active or non active)
Hepatocellular carcinoma
Liver cirrhosis.
Portal hypertension.
Liver cell failure.

9. Acute Hepatitis B infection
Virulent strain of hepatitis, Co-infection (HDV), Uncontrolled immunity and cytokines
Limited cell-mediated and humoral immunity
Effective cell-mediated and humoral immunity (Anti HBs antibodies)
Chronic stage; Asymptomatic carrier
Chronic active hepatitis
Minimal chronic hepatitis (persistent, fluctuating)
Resolution
Fulminant Hepatitis
Liver Cirrhosis
Hepatocellular Carcinoma

10. Diagnosis of Hepatitis B infection:
In incubation period and pre-icteric phase: The first indicators are HBV DNA, HBs Ag and HBe Ag (envelope).
In acute icteric phase: Elevated bilirubin (total & direct), liver enzymes (transaminases), bilirubinuria, elevated HBc IgM antibodies in serum.
In Convalescence phase: HBs Antibodies (neutralizing) elevates in serum (positive).
In Chronic period after 6 months:
HBs Ag: positive
Anti-HBs Antibodies: negative.
Anti-HBc IgG Antibodies: positive

12. Diagnosis of Hepatitis B infection:Ni

13. Treatment:
Interferon-α therapy.
lamivudine or adefovir:
Prevention:
Active vaccine: HBs Ag (recombinant vaccine) safe can be given to infants, health care workers. prevent both HBV and HDV.
Passive vaccine: human Anti-HBs (exposed persons; needle stick, infants born to seropositive mother, sexual) within 48 hours from exposure.

14. Hepatitis C Virus Infection:
Pathogenesis:
Replication of virus in hepatocytes, lymphocytes, and macrophages.
Destruction of cells by the virus and immunity.

15. Clinical outcomes of acute hepatitis C infection:
Subclinical infection in 75% of cases
Acute hepatitis C (25% of cases)
Resolution of disease (months)
Chronic hepatitis C (10-15 years)
Cryoglobulins are single or mixed immunoglobulins that undergo reversible precipitation: arthritis, enlargement of the spleen, skin vasculitis with purplish patches, and nerve and kidney disease.
Mixed Cryoglobulinemia:*
Arthritis, purpura, glomerulonephritis
Cirrhosis (20%)
Hepatocellular Carcinoma
Liver failure

16. Detection of viral RNA in serum by quantitative RT-PCR technique.
Diagnosis of HCV:
Detection of Anti-HCV recombinant viral protein antibodies in patient serum by ELISA or RIBA.
Detection of viral RNA in serum by quantitative RT-PCR technique.
Treatment and Prevention:
Combination therapy of interferon-α and ribavirin .
Newer drugs as sovaldi.
No available vaccine. N

17. Clinically (4 weeks): fever, jaundice, vomiting nausea.
Hepatitis A infection
Pathogenesis:
Food → intestine → portal vein → liver .
Replicate in hepatocytes excreted in bile ducts → stool → faco-oral infection.
Released in bloodstream → transient viremia.
Clinically (4 weeks): fever, jaundice, vomiting nausea.
Diagnosed: by HAV IgM & HAV IgG (neutralizing)
Vaccines:
Inactivated vaccine.
Post-exposure prophylaxis (Anti-HAV).

18. Other causative agents for liver infection:
Bacterial infections: Liver abscesses formation.
Intra abdominal infection; portal-vein bacteremia;
Hepatic artery bacteremia; systemic infection.
Ascending cholangitis:
E.coli is the most frequent agent of cholangitis.
40% of the cholangitis are caused by mixture of facultative anaerobic and obligate anaerobic ascends from the duodenum.

19. Parasitic Liver Infections:
Leishmaniasis.
Extra-intestinal amoebiasis.
Schistosomiasis.
Malaria.
Leishmaniasis: Leishmania donovani
- Visceral leishmaniasis (Kala-azar); jaundice, inverted albumin/globulin ratio.
- In liver: intracellular amastigote stage.

20. Leishmania donovani amastigote form inside Kupffer cells in the liver

21. Malaria: Plasmodium formation of liver Schizonts.
Extra-intestinal Amebiasis: Entamoeba histolytica. Causes hepatic cyst & abscess due to transfer of trophozoite via portal system.
Schistosomiasis: Schistosoma mansoni; Schistosomula migrates to venous system of liver then to venous plexuses of large intestine Damage in liver: Egg-Granulomas in portal area Pipe stem fibrosis of portal tracts.
Malaria: Plasmodium formation of liver Schizonts. N