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
(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
Clinical outcomes
of Chronic Infection NO
Cirrhosis or
hepatocellular carcinoma
Co-infection 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:
Interferon-α production; Up-regulates MHC-I expression and inhibits viral replication cycle.
Kupffer cell response; release of cytokines and inflammatory mediators; chemotaxis.
Infection of hepatocytes activate T-cell mediated cytotoxicity: interaction between hepatocyte- MHC-I + HBc Ag or HBe Ag fragments and CD8.
Enhanced natural killer cell activity; cytotoxicity.
HBs Ag & anti-HBs Ag antibodies complexes activate complement system; damage.

7. Clinical presentation of hepatitis B infection:
Incubation period: days.
Acute infection period:
A- Pre-icteric phase: (days to week): mild fever, anorexia, myalgia, and nausea.
B- Icteric acute phase:(one to two 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; high fever, abdominal pain, renal dysfunction, encephalopathy (lethal in 8% of cases).

8. Chronic infection:
Chronic asymptomatic carrier
Chronic persistent hepatitis
Chronic active hepatitis

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 indicator is HBs Ag and HBe Ag (envelope).
In acute icteric phase: Elevated bilirubin (total & direct), liver enzymes (transaminases), bilirubinuria, elevated anti-HBc antibodies in serum.
In convalescence phase: Anti-HBs Antibodies starts elevation in serum (positive).
In chronic period:
HBs Ag: positive
Anti-HBs Antibodies: negative.
Anti-HBc Antibodies: positive
The rationale for treatment in patients with chronic HBV is to reduce the risk of progressive chronic liver disease, transmission to others, and other long-term complications from chronic HBV such as cirrhosis and hepatocellular carcinoma.
We recommend that treatment be considered in patients with HBeAg positive or HBeAg negative chronic hepatitis

12. Diagnosis of Hepatitis B infection:Ni

13. Treatment and Prevention:
Reduction or elimination of HBV replication indicators can be achieved by Interferon-α therapy.
Antiviral-nucleoside analogs that given orally have similar effect on viral replication (lamivudine or adefovir: inhibition of viral reverse transcriptase).
Prevention:
Active vaccine: HBs Ag (children vaccination or others) which prevent both HBV and HDV.
Passive vaccine: Serum Anti-HBs (exposed persons; needle stick, infants born to seropositive mother, sexual)

14. Hepatitis C Virus Infection:
90% of cases of non-A, non-B hepatitis.
Transmission:
post- transfusion hepatitis.
Intravenous drug users
Patients on hemodialysis.
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 nucleic acid in serum by RT- PCR technique.
Diagnosis of HCV:
Detection of Anti-HCV recombinant viral protein antibodies in patient serum by ELISA.
Detection of viral nucleic acid in serum by RT- PCR technique.
Treatment and Prevention:
Combination therapy of interferon-α and ribavirin provides a significant response (30- 50% for genotype 1 and 70-75% for viral genotype 2 and 3).
No available vaccine. N

17. Hepatitis A infection:
Responsible for most cases of infectious hepatitis.
Non-enveloped SS-RNA Virus.
Transmission: fecal-oral or contaminated water.
Pathogenesis:
Enter blood from intestine; portal system; liver.
Replicate in hepatocytes (destruction), excreted through bile ducts into stool (a high titer =1011 virion/ml)
Released in bloodstream (to a lesser extent); transient viremia.
Vaccines:
inactivated vaccine (cell-cultured).
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 mix facultative anaerobic and obligate anaerobic ascends from the duodenum.

19. Parasitic Liver Infections:
Leishmaniasis.
Extra-intestinal amebiasis.
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 & abcess 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