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Hepatitis:
Hepatitis is the inflammation of liver caused by immune
response against : liver parenchyma induced by viral
infections, or some intracellular pathogens that survive in
Kupffer cells causing granulomatous infections (Typhoid
fever, brucellosis, Q fever, T.B).
Liver abscesses:1-Portal Vein Bacteremia. 2-Hepatic Artery Systemic Bacteremia.3-Ascending Cholangitis.
N
Viral causative agents for hepatitis are:
1- Professional-hepatitis viruses:
Hepatitis A,B,C,D, and E; strong tropism to hepatocyte.
2-Non-Professional viruses that cause extra-hepatic
diseases:
Yellow fever viruses, E.B virus secondary to I.M,
CMV, adenovirus, Herpes simplex, and VZV.
Hepatitis Viruses: Hepatitis A, B, C, D, and E:N
Type Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Mode of Transmission
Fecal-Oral BloodborneSexualVertical
BloodborneSexualVertical
BloodbornSexualVertical
Fecal-Oral
Classification& genetic material
Picornaviridae.Linear SS-RNA
Hepadnaviridae.Circular DS-DNA-R.T enz
Flaviviridae
Linear SS-RNA
Deltaviridae.Circular SSRNA
Caliciviridae
Linear SS-RNA
Incubation &Chronic infection
15-40 daysNO.
60-180 daysYES(5%)
60-120 daysYES (80%)
60-180 daysYES
21-42 daysNO.
Clinical outcomesof Chronic Inf
NO Cirrhosis or Hepatocellul-ar Carcinoma
Cirrhosis or Hepatocellul-ar Carcinoma
Co-infection
NO
Hepatitis B virus: Pathogenesis:-Infection of hepatocytes.-T-cell mediated cytotoxicity: interaction between hepatocyte-MHC class I-HBcAg or HBeAg fragments and CD8+-TCR.-Kupffer cell response; release of cytokines and inflammatory mediators; chemotaxis. -Enhanced natural killer cell activity; cytotoxicity. -Interferon-α production; Up-regulates MHC-I expression and inhibits viral replication cycle.-HBsAg/Anti-HBsAg Antibodies complexes activate complement system damage.
Clinical presentation of Hepatitis B infection:
-Incubation period.-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): Much more extensive necrosis of liver during icteric phase; elevated fever, abdominal pain, renal dysfunction, Lethal in 8% of cases.
n
N
Acute Hepatitis B infection
Effective cell-mediated and humoral immunity
Resolution
Limited cell-mediated and humoral immunity
Chronic stage;
Asymptomatic carrier Chronic active
hepatitis
Liver Cirrhosis Hepatocellular Carcinoma
Minimal chronic
hepatitis (persistent)
Virulent strain of hepatitis, Co-infection (HDV),
Uncontrolled immunity and
cytokines
Fulminant Hepatitis
Diagnosis of Hepatitis B infection:
-In incubation period and pre-icteric phase: The first indicator is HBsAg and HBeAg (envelope).-In acute icteric phase: Elevated Bilirubin(T,D), 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-HBc Antibodies: positive Anti-HBs Antibodies: negative.
Diagnosis of Hepatitis B infection:Ni
Treatment and Prevention:
-Reduction or elimination of HBV replication indicators
could be performed by Interferon-alpha therapy.
-Antiviral-nucleoside analogs that given orally have
similar effect on viral replication (Lamivudine or adefovir:
inhibition of viral reverse transcriptase).
Prevention: 1-Active vaccine: HBsAg (children vaccination or others).2-Passive vaccine: Serum Anti-HBsAg (exposed persons; needlestick , infants born to seropositive mother, sexual)
Hepatitis C virus infection:
HCV accounted for ninety percent of cases of non-A, non-B hepatitis. Transmission: 1-It was initially identified as a major cause of post- transfusion hepatitis. 2-Intravenous drug users 3-Patients on hemodialysis. 4-Sexual route, and vertical.
Pathogenesis: -Replication of virus in hepatocytes, lymphocytes, and macrophages.-Destruction of cells by viral replication cycle and immunity.
Clinical outcomes of acute hepatitis C infection:N
Acute hepatitis C infection
Subclinical infection in 75% of cases
Chronic hepatitis C (10-15 years)
Acute hepatitis C (25% of cases)
Resolution of disease (months)
Cirrhosis (20%) Hepatocellular
Carcinoma Liver failure
Mixed Cryoglobulinemia
N
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 significantly improved response ( 30-50% for genotype 1
and 70-75% for viral genotype 2 and 3).
-No available vaccine.
Hepatitis A infection:
-HAV is responsible for most cases of infectious hepatitis.-Non-enveloped SS-RNA Virus.-Transmission: Fecal-Oral route or contaminated water.-Pathogenesis:-Absorbed into bloodstream by intestine; portal system of liver.-Replication in hepatocytes; destruction, exported into bile ducts; excreted into stool ( a high titer=1011 viron/ml)-Released in bloodstream (to a lesser extent); transient viremia. -Acute hepatitis; inactivated vaccine (cell-cultured). Post-exposure prophylaxis (Anti-HAV-Abs).
Other causative agents for liver infection:
Bacterial infections: Liver abscesses formation.1-Portal-vein bacteremia.2-Hepatic artery bacteremia.3-Ascending cholangitis; E.coli is the most frequent agent 40% Facultative anaerobic and obligate anaerobic ascends from the duodenum.
Several Parasitic infections:1-Leishmaniasis: Leishmania donovani ; Visceral leishmaniasis (Kala-azar); jaundice, A/G ratio. In liver: intracellular Amastigote stage.
N
2-Extra-intestinal Amebiasis: Entamoeba histolytica Causes hepatic cyst due to transfer of trophozoite via portal system.
3-Schistosomiasis: Schistosoma mansoni; Schistosomula migrates to venous system of liver then to venous plexuses of large intestine. In liver: Egg-Granulomas in portal area. Pipe stem fibrosis of portal tracts.
4-Malaria life cycle: Plasmodium causes liver Schizonts.