VIRAL HEPATITISAcute hepatitis Chronic hepatitis- Inflammation of liver parenchyma that resolves within 6 months after infectionDefiniton- Liver inflammation that last for 6 months or longer- Viral infections : hepatitis A, B D, C, Cytomegalovir!s pstein-Barr vir!s "erpes simple# $ellow fever- Dr!g- in%!ce% liver in&!ry: paracetamol- A!toimm!ne hepatitis- 'on-viral infection: (o#oplasma gon%ii, leptospira,co#iella )!rnettii- Alcohol- *oison: Amanita phalloi%es +m!shrooms,, Aflato#in, Car)on tetrachlori%e- -thers: pregnancy, circ!latory ins!fficiency, .ilson/s %iseasetiology- Viral: "epatitis B, C- Dr!gs: 0ethyl%opa, Isonia1i%,2etocona1ole,'itrof!rantoin- "ere%itary: .ilson/s %isease- -thers: Inflammatory )owel %isease li3e 4lcerative colitis- "epatocyte in&!ry with cell %eath, inflammation an% regeneration witho!t str!ct!ral change to the liver- #tent of %amage : varies from only single an% small gro!p of hepatocytes %ie +focal necrosis, to m!lti-acinar necrosis involving s!)stantial part of liver +massive hepatic necrosis, *athologyCharacteri1e% )y:- *ortal tract inflammation- Interface hepatitis- *ortal-)ase% fi)rosis, )ri%ging fi)rosis or cirrhosis- Also lo)!lar inflammation an% apoptosis- Ac!te liver fail!re- Cholestatic hepatitis +hep A,- Aplastic anaemia- Chronic liver %isease an% cirrhosis +hep B, C,- 5elapsing hepatitisComplications- Liver fail!re- *ortal hypertension- Coag!lopathy- "ypoal)!minaemia- "epatorenal syn%rome- Liver cirrhosisACUTE HEPATITIS Clinical 6eat!res: - 'on-specific pro%romal illness: hea%ache, myalgia, arthralgia, na!sea, anore#ia- 7a!n%ice : few %ays to 8 wee3s- Vomiting, %iarrhoea- A)%ominal %iscomfort- Dar3 !rine, pale stools- Liver ten%erness, minimally enlarge%- 0il% splenomegaly, cervical lympha%enopathyInvestigations:- Liver f!nction tests: ser!m transaminases )etween 899 an% 8999 4:L +lower in chronic,- *lasma )ilir!)in, AL* increase%- *rolonge% prothrom)in time- .hite cell co!nt: relative lymphocytosis- ;erological test to confirm aetiology of infection 1. HEPATITIS AEpidemiologyInvestigations Managements- *icornavir!s gro!p of enterovir!s- (ransmission )y faeco-oral ro!te- Infecte% in%ivi%!al may )e asymptomatic, )!t e#crete the vir!s in faeces for a)o!t 8-< wee3s )efore the onset of symptoms- Common in chil%ren )!t often asymptomatic, common in areas of overcrow%ing an% poor sanitation- In o!t)rea3s: water an% shellfish have )een vehicles of transmission- 'o chronic carrier state- Ac!te liver fail!re is rare in hepatitis A- Anti- "AV anti)o%y is important as "AV is only present in )loo% transiently %!ring inc!)ation perio%= anti-"AV +Ig0 type, in%icating a primary imm!ne response th!s is a%iagnostic of an ac!te "AV infection= fall to lowlevels within a)o!t < months of recovery, anti-"AV +Ig> type,is no %iagnostic val!e as "AV infection is common )!t can )e !se% as a mar3er of previo!s infection, in%icates imm!nity to "AV- #cretion of vir!s in stools occ!r only ?-@A %ays after onset of the clinical illness, cannot )e grown rea%ily- Can )e prevente% )y improving social con%itions- ;!)stantial protection )y active imm!nisation with an inactivate% vir!s vaccine for those in partic!lar ris3 +close contacts of "AV- infecte%patients, the el%erly, thosewith other ma&or %isease, pregnant women,- Antiviral %r!gs has no role2. HEPATITIS Epidemiology Investigations Managements--ne of the most common ca!ses of chronic liver %isease an% hepatocell!larcarcinoma- Ac!te infection is often asymptomatic, partic!larlywhen acB!ire% at )irth, many in%ivi%!als with chronic infection also asymptomatic- (he ris3 of progression to chronic liver %isease %epen%s on the so!rce an%timing of infection- ;o!rce of "ep B infectionan% ris3 of chronic infection: "ori1ontal transmission +@9C,: %r!g !ser in&ection, infecte% )loo% pro%!cts, tattoo or nee%le p!nct!re, se#!al contact, close living= vertical transmission +D9C, = "BsAg-positive mother- Chronic hepatitis can lea% to cirrhosis or "CC- Vir!s is not %irectly cytoto#ic to cells, rather isis an imm!ne response to viral antigens %isplaye% on infecte% hepatocytes that initiates liver in&!ry@E ;erology - "BV contains several antigens an% their anti)o%ies are important in i%entifying the infection- "BsAg is an in%icator of active infection= appear late in the inc!)ation perio%, )!t)efore the pro%romal phase=present for a few %ays only an% %isappear even )efore &a!n%ice %evelope%= lasts for , in the )loo%8E Viral loa% an% genotype- *C5: meas!re viral D'A levels in peripheral )loo%= e#cess of @9F copies:ml in presence of active replication +"BeAg,@E Ac!te hepatitis B- ;!pportive with monitoring for ac!te liver fail!re- 'o %efinitive evi%ence that antiviral therapy re%!ces the severity or %!ration of infection- 6!ll recovery occ!rs in D9-DFC of a%!lts within 6 months, F-@9C %evelop a chronic hepatitis B infection +vertical transmission recovery is rare,8E Chronic hepatitis B- (reatments are still limite%, no %r!g is consistently a)le to era%icate infection completely- (he goals are "BeAg seroconversion, re%!ction in "BV-D'A an% normalisation of the L6(s- In%ication: high viral loa% in the presence of active hepatitis- Direct-acting n!cleosi%e: n!cleoti%e antiviral agents= inhi)iting the reverse transcription of pre-genomic 5'A to "BV-D'A )y "BV-D'A polymerase )!t not cccD'A +relapse is common,= lamiv!%ine, entecavir an% tenofovir- Interferon-alpha= most effective in patient with low viral loa% an% ser!m transaminases greater thantwice= si%e effects are common- Liver transplantation with post-transplant prophyla#is- A recom)inant hep B vaccine!. HEPATITIS CEpidemiology Investigations Managements-Ca!se% )y 5'A flavivir!s- Ac!te symptomatic infection is rare, most in%ivi%!al remains asyptomatic !ntil progression to cirrhosis occ!r- G9C of the e#pose% )ecome chronically infecte% an% late spontaneo!s viral clearance is rare- "ep C is ca!se ofHnon-A, non-B hepatitisI- 5is3 factors of chronic hep C infection: intraveno!s %r!g mis!se, !nscreene% )loo% pro%!cts, vertical transmission, nee%lestic3 in&!ry, iatrogen!c parenteral transmission, sharing tooth)r!shes:ra1ors@E ;erology an% virology- "CV protein antigens give rise to anti)o%ies thatmay )e appear in )loo% a)o!t 6-@8 wee3s following ac!te infection- "ep C 5'A in the )loo% as early as 8-A wee3s after infection- Active infection: presenceof ser!m hep C 5'A in anyone who is anti)o%y positive- Anti-"CV anti)o%ies persist even after viral clearance8E 0olec!lar analysis- ;i# common genotypes- >enotypes has no effect on progression )!t %oes affect response to treatment- >enotype @ is common innorthern !rope an% is less easy to era%icate thangenotypes 8 an% < with tra%itional pegylate% interferon alpha:ri)avirin-)ase% treatement