18-3-2014 sheet number :13 done by : Enas Al-Hawari

Hepatitis B virus :

-Main different from other virus is the most common viral hepatitis worldwide ( highest prevalence ).

-highly effective .

- high infectivity rate

- number of virus is low

-resist extreme condtion witout denaturation .

-incubation period ( viremia ) longer than other (1-4) months

- present in all phsiologic and pathologic fluidsexpect for stool , also important cause of parental , sexual, perinatal infection .

Clincal course >>> highly inffective so most of patients they recover , 60% subclinical infection “ silent infection ,, come then recover “

Acute hepatitis >> 20% most of them recover .

Carrier (5-10)% >> silent “ no disease.. stable disease “ but it is infective .

5% >> chronic hepatitis either recover or continue to cirrohosis or cancer .

HBV structure :

Important to know structure because it important for dignosis and vaccination .

Multiple Ag for hepatitis B virus and each Ag have antibody .

1- Core “c” Antigen >> restrict inside hepatocyte (doesn’t go to blood ), so cant test hepatits core Ag , but you can test AB ,, this core Ag part of virus so present in all stage when enter the body ( in active , silent , chronic phase ) >> in all these phase core Ag present .

2- “e” antigen >> more important than c Ag , produce when virus is active ( patient have real hepatitis ) so disease is active , reflect infectivity mean

18-3-2014 sheet number :13 done by : Enas Al-Hawari

the infection work in patients ,, also can secret in blood so can test it “ you can ask to check for Ag and AB “ .

We know AB reflect past infection but could be active or inactive(past infection ) ?? cant no so not specific … but Ag if present mean active .

3- S antigen “ surface antigen “ >> resemble core Ag but secret in blood , when virus enter so Ag present in the body ,, surface Ag is outside Ag so can be use as vaccination …. Hepatitis B vaccine is surface Ag >> all medical field must take it .** if measure it in the blood >> postive surface !! what mean ?? maybe have infection active or past infection or maybe just vaccine , so must test multiple immunoglobulin and Ag to know the exact status of virus .

4- x protein >> gust un pathophysiology not in diagnosis ,, transcripation factor important for infective and neoplastic development , as hepatitis A virus >> virus incorporated inside the cell but not cause damage “ enter inside without make lysis , damage , or any destruction … Damage mainly due to immune system >> because recognize it as forign body .** Chart in page 11 :Left side > active disease this one develop into chronic .Hepatitis e Ag >> less infectivity ( more in serum ) ,,, hepatitis B DNA can measure in serum ,,, surface Ag present already . “”all in blood “”” Core Ag inside hepatocyte not present in blood . Serum transaminase “” increase due to damage to hepatocyte “”Lines >> represent immunoglobulin >>> IgG : continue all the life ,,, IgM :reflex acute phase .Chronic disease Ag persist ,,, E Ag serum is present al the time the same as DNA ,, HBS Ag .** symptoms: mainly chronic phase active but can be silent or carrier , symptom remove but disease still there .Conclusion : outcome most of patient recover “ most of patient subclinical “ ,, 20% active hepatitis but will recover ,,, 10%silent carrier , 5% chronic hepatitis .

18-3-2014 sheet number :13 done by : Enas Al-Hawari

Hepatitis C :- B and C more important .- Hepatitis c more dangerous in general “ infective less but disease more

significant “ ,,more limited than HBV - Single strand RNA virus .- Way of transmission >> parentally by fluid ( blood , serum ) no feco-oral

route ,, no vertical transmission “ from mother to fetus “- Major root of transmission by blood >> blood contamination due to

injury any cutting ,, also direct fluid injury ,, IV drug abuse as use of syringe after infected patient ,, also exposure to saliva as our job in future we all risk of transmission of the disease .

- Incubation period less than B (2-26) weeks “ variable ..it long time - Clinical course : make chronic not acute hepatits ,,,, mostly become

chronic ( persistant ) so 75% of infective patient have silent disease firstly also less manifestation ,detected by routine test for liver enzyme “ elevated “ 80% develop into chronic phase but hepatits B chronic 5% ** greater risk for hepatocellular carcinoma and cirrhosis .

- Diagnosis difficult ?? no benefit from serology ,,,detect by DNA through PCR ( polymerase chain reaction )detect DNA or RNA.

- Just 15% which immune system can defend .- Fulminant hepatitis” make acute damage and acute hepatic failure >>

very rare “ difference from other >>> here go to chronic not as hepatitis A,E>> acute hepitits.

- Must of patient go to chronic hepatitis >> 80% stable disease and 20% continue to cirrhosis and hepatocellular carcinoma .Hepatitis D virus :

- Unique one ,,, a virusoid >> small virus not complete virus “ follower cant work alone just with presence of hepatitis B .

- Defective circular RNA particles .- If two pattern occur at same time contamination this called coinfection

: 10% develop chronic hepatitis ,, remember B 5% become chronic .

18-3-2014 sheet number :13 done by : Enas Al-Hawari

Superinfection : more significant , patient have chronic active B virus then affected by D virus “ hepatits D when superimposed chronic active B virus “ ,, here 70% develop chronic hepatitis or severe disease .Hepatitis E virus :

- Resemble A virus but much less prevelant .- Single stranded RNA virus .- Transmitted through contimnated food and water “ feco – oral “ - Never develop into chronic hepatitis . - Mild , self limited as A ,,, BUT EXCEPTION : cause hepatitis in pregnant

women

-Risk of complication high not as hepatits A virus .

Fulminant hepatitis :

-Most severe form of liver disease , sever inflammation at entire liver cause acute hepatitis failure not chronic “ all liver inflamed and damage ,,, also secondary to massive hepatocyte necrosis …

-Any pain can cause fulimant hepatitis ,, have variable complication rate for example C >> unusual ,, E>> pregnant women can cause fulminant hepatitis .

*Drug : in reye syndrome due to aspirin can form fulimnat hepatitis as child die from this complication … also halothane “in anesthesia “>> some patient have” endure syndetic rxn “sensitive so cause liver damage “ fulminant “ then die … also paracetamol if person take high dose cause hepatocellular necrosis .* toxin very common . * viral hepatitis A,B,E “D with B” ,C unusual .

** morphology :

Grossly : liver enlarge ?? due to edema , inflammatory cells

18-3-2014 sheet number :13 done by : Enas Al-Hawari

Cholestatic (because function of hepatocyte to conjugate bilirubin and excret it ,, if this function disrupt this make cholestatic “accumulation of builirubin “ so appear as green in color .Microscope : cell injury in hepatocyte become swelling “ balloone “ also foam cytoplasm then occur damage “necrosis “,, shrinkage “ small” , dark in color …. Cholestatic : bile pigment ..

-Influx of lymphocyte and monocyte also macrophage >>>> inflammatory cell “all prevalent in hepatocyte “

-Portal inflammation >> variable “ hepatitis c make more damage to portal area “

-More sever >> more bridiging inflammation and necrosis “ involve region far away “.

-At the end stage make cirrhosis (nodules instead of normal structure of liver” longitudinal plates”).

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Here biopsy from acute viral hepatitis case :

*most prevalent >> inflammatory cell “ very dark and small “ >> ex: macrophage , lymphocyte they are very prevelant in liver parenchyma .

Be attention to arrow >>> dark in color and shrinkage this called apoptitc body .”scatter “

18-3-2014 sheet number :13 done by : Enas Al-Hawari

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here hepatitis C virus >> go to portal area in order to destroy it ,, we know portal area round also here no bile duct , no artery ,, no vein just occupy by lymphocyte , in the peripheries fibrosis acellular part “ empty” ….. lymphocyte very big make nodules in portal area .

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Here from hepatitis B :

Concentrate inside cytoplasm , particles present inside cytoplasm ..cytoplasm large special color called ground glass hepatocyte as broken glass which appear as small particle shiny … due to accumulation of HBsAg “ viral particles

Arrow >> portal tract expansion with inflammatory cell and fibrous tissue .

18-3-2014 sheet number :13 done by : Enas Al-Hawari

In advance stage , grossly the shape of liver all nodules cirrhosis instead of normal particles also total liver size reduce “ shrinkage “ .

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Autoimmune hepatitis :

-Inflammatory disease .

-from name: immune derangement in the body “ no viral inflammation it is chronic disease , so exclude all virus especially C,B so patient free from (C,B) but patient have active hepatitis .

Same symptoms and morphology : - severe inflammatory cell in liver parenchyma

-damage

- apoptitic and necrotic cell

- ballooning

- fibrosis which develop cirrhosis

* non viral >> so viral screening is negative .

Foamy cytoplasm “balloone “

18-3-2014 sheet number :13 done by : Enas Al-Hawari

- associated with other autoimmune diseases ex : rheumatoid arthritis ,,, hashimoto thyroiditis >>> mainly in female “ have multiply autoimmune diseases one of them hepatitis .

- one of criteria >> resepond to immune suppression ex: steroid ,, when give suppress the immune system so hepatitis subside

- female predominant 70%

- immunoglobulins are high >> inflammatory cell all work one of them B cell which secret Immunoglobulin so total number increase in body especially IgG very high .

- 5% resist treatment develop into cirrhosis .

Good luck …..

Sorry for any mistakes ….