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.